Is MEFV p.Pro115Arg (c.344C>G) pathogenic?

MEFV p.Pro115Arg (c.344C>G) is classified Conflicting classifications of pathogenicity in MEFV (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-11-27). AlphaMissense: likely benign (0.0861); Rare (popmax 0.25%, eas); Associated with familial Mediterranean fever.

What condition is associated with MEFV p.Pro115Arg (c.344C>G)?

MEFV p.Pro115Arg (c.344C>G) is associated with familial Mediterranean fever (ClinVar).

How common is MEFV p.Pro115Arg (c.344C>G) in the general population?

MEFV p.Pro115Arg (c.344C>G) is rare (popmax 0.25%, 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.Pro115Arg (c.344C>G)?

AlphaMissense predicts likely benign (score 0.0861) — an in-silico prediction, not a clinical call.

MEFV p.Pro115Arg

c.344C>G · rs201766654 · VCV763253

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0861 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.25%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

familial Mediterranean fever

Computational evidence

Protein change
AlphaMissense	0.0861	likely benign
REVEL	0.27	benign-leaning
SaProt	LLR -7.62	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 1.4	GERP -4.1, phastCons 0.47
Regional constraint	o/e 1.16	unconstrained · MANE · 13 kb · p 2.1e-07 · regional, not allelic
Overall
CADD	11.14	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 0.25% East Asian · 112/44,886 alleles

Filtering AF 0.212% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.198%

Overall 0.00707% 114/1,612,868 alleles · rare exomes 106/1,460,506 · genomes 8/152,362 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.25%	401
Remaining individualsnot grpmax-eligible	0.0032%	31,246

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.Pro115Arg
Coding: c.344C>G
MANE Select: NM_000243
dbSNP: rs201766654
Type: single nucleotide variant
Location: chr16:3254724 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 73.64 · 11 PDB
Residue 115: the 'disordered' region

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

Disease context

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

For Familial Mediterranean fever (Orphanet):

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

Similar variants

MEFV p.Pro115Ser Uncertain significance ★★ ⚠ same residue
MEFV p.Pro115Thr Conflicting classifications of pathogenicity ★ ⚠ 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-pro115arg (accessed [today's date]).

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