Is MEFV p.Arg80His (c.239G>A) pathogenic?

MEFV p.Arg80His (c.239G>A) is classified Conflicting classifications of pathogenicity in MEFV (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2024-06-19). AlphaMissense: likely benign (0.0789); Ultra-rare (popmax 0.0401%, eas); Associated with familial Mediterranean fever, autosomal dominant.

What condition is associated with MEFV p.Arg80His (c.239G>A)?

MEFV p.Arg80His (c.239G>A) is associated with familial Mediterranean fever, autosomal dominant, sweet syndrome, familial Mediterranean fever (ClinVar).

How common is MEFV p.Arg80His (c.239G>A) in the general population?

MEFV p.Arg80His (c.239G>A) is ultra-rare (popmax 0.0401%, eas) (gnomAD).

How is Familial Mediterranean fever inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about MEFV p.Arg80His (c.239G>A)?

AlphaMissense predicts likely benign (score 0.0789) — an in-silico prediction, not a clinical call.

MEFV p.Arg80His

c.239G>A · rs201075710 · VCV633298

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0789 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0401%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

familial Mediterranean fever, autosomal dominant

Computational evidence

Protein change
AlphaMissense	0.0789	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -4.75	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP -0.029, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 13 kb · p 2.1e-07 · regional, not allelic
Overall
CADD	16.53	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0401% East Asian · 18/44,878 alleles

Filtering AF 0.0259% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0214%

Overall 0.00198% 32/1,613,948 alleles · ultra-rare exomes 27/1,461,624 · genomes 5/152,324 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0401%	2,493
Admixed American	0.00333%	30,007
South Asian	0.0022%	45,538
Remaining individualsnot grpmax-eligible	0.0016%	62,498
European (non-Finnish)	0.000763%	131,114

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: MEFV
Protein: p.Arg80His
Coding: c.239G>A
MANE Select: NM_000243
dbSNP: rs201075710
Type: single nucleotide variant
Location: chr16:3256349 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 73.64 · 11 PDB
Residue 80: the pyrin domain; an α-helix

Full MEFV gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

familial Mediterranean fever, autosomal dominant — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: sweet syndrome familial Mediterranean fever

For Familial Mediterranean fever (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy
Prevalence: >1 / 1000 (Turkey)

Similar variants

MEFV p.Arg80Cys Uncertain significance ★★ ⚠ same residue
MEFV p.Arg80= Likely benign ★ same residue
MEFV p.Arg761His Pathogenic/Likely pathogenic ★★ ⚠ same condition
MEFV p.Ser242Arg Pathogenic/Likely pathogenic ★★ same condition
MEFV p.Val726Ala Pathogenic/Likely pathogenic ★★ ⚠ same condition
MEFV c.*845C>T Uncertain significance ★★ same condition
MEFV p.Ala193Thr Uncertain significance ★★ ⚠ same condition
MEFV p.Ala2Gly Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/mefv-p-arg80his (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown