Is MEFV p.Arg151Ser (c.453G>C) pathogenic?

MEFV p.Arg151Ser (c.453G>C) is classified Uncertain significance in MEFV (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-01-01). AlphaMissense: likely benign (0.2457); Ultra-rare (popmax 0.0386%, sas); Associated with sweet syndrome.

What condition is associated with MEFV p.Arg151Ser (c.453G>C)?

MEFV p.Arg151Ser (c.453G>C) is associated with sweet syndrome, familial Mediterranean fever, autosomal dominant, familial Mediterranean fever (ClinVar).

How common is MEFV p.Arg151Ser (c.453G>C) in the general population?

MEFV p.Arg151Ser (c.453G>C) is ultra-rare (popmax 0.0386%, sas) (gnomAD).

How is Sweet syndrome inherited?

Typically Multigenic/multifactorial (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about MEFV p.Arg151Ser (c.453G>C)?

AlphaMissense predicts likely benign (score 0.2457) — an in-silico prediction, not a clinical call.

MEFV p.Arg151Ser

c.453G>C · rs104895185 · VCV97524

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.2457 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0386%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

sweet syndrome

Computational evidence

Protein change
AlphaMissense	0.2457	likely benign
REVEL	0.206	benign-leaning
SaProt	LLR -5.88	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 -2.2	GERP -4.1
Regional constraint	o/e 1.16	unconstrained · MANE · 13 kb · p 2.1e-07 · regional, not allelic
Overall
CADD	1.621	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0386% South Asian · 35/90,738 alleles

Filtering AF 0.0284% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.025%

Overall 0.00256% 41/1,603,124 alleles · ultra-rare exomes 37/1,450,784 · genomes 4/152,340 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0386%	2,593
Remaining individualsnot grpmax-eligible	0.00805%	12,421
European (non-Finnish)	8.5e-05%	1,176,887

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.Arg151Ser
Coding: c.453G>C
MANE Select: NM_000243
dbSNP: rs104895185
Type: single nucleotide variant
Location: chr16:3254615 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 73.64 · 11 PDB
Residue 151: the 'disordered' region

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

Disease context

sweet syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial Mediterranean fever, autosomal dominant familial Mediterranean fever

For Sweet syndrome (Orphanet):

Inheritance: Multigenic/multifactorial
Onset: Adult

Similar variants

MEFV p.Arg151Gly Uncertain significance ★ ⚠ same residue
MEFV p.Arg151Trp Uncertain significance ★ ⚠ same residue
MEFV p.Arg151= Likely benign ★ same residue
MEFV p.Arg151fs Uncertain significance ★ same residue
MEFV p.Arg151Thr Uncertain significance ★ ⚠ 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

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-arg151ser (accessed [today's date]).

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