Is MEFV p.Gln424Pro (c.1271A>C) pathogenic?

MEFV p.Gln424Pro (c.1271A>C) is classified Uncertain significance in MEFV (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-19). AlphaMissense: likely pathogenic (0.6252); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with MEFV p.Gln424Pro (c.1271A>C)?

MEFV p.Gln424Pro (c.1271A>C) is associated with Inborn genetic diseases (ClinVar).

How common is MEFV p.Gln424Pro (c.1271A>C) in the general population?

MEFV p.Gln424Pro (c.1271A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MEFV p.Gln424Pro (c.1271A>C)?

AlphaMissense predicts likely pathogenic (score 0.6252) — an in-silico prediction, not a clinical call.

MEFV p.Gln424Pro

c.1271A>C · rs1958989052 · VCV2619360

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6252 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6252	likely pathogenic
REVEL	0.167	moderately benign-leaning
SaProt	LLR -10.04	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 0.96, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 13 kb · p 2.1e-07 · regional, not allelic
Overall
CADD	19.92	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MEFV
Protein: p.Gln424Pro
Coding: c.1271A>C
MANE Select: NM_000243
dbSNP: rs1958989052
Type: single nucleotide variant
Location: chr16:3248994 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 73.64 · 11 PDB
Residue 424: an α-helix; the 'required for homotrimerization and induction of pyroptosomes' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MEFV p.Cys332Tyr Uncertain significance ★★ ⚠ same condition
MEFV p.Gly137Ser Uncertain significance ★★ ⚠ same condition
MEFV p.Ser331Phe Uncertain significance ★★ ⚠ same condition
MEFV p.Ala457= Likely benign ★★ same condition
MEFV p.Ala497= Likely benign ★★ same condition
MEFV p.Gln476= Benign/Likely benign ★★ same condition
MEFV p.Gln753= Likely benign ★★ same condition
MEFV p.Tyr60= Benign/Likely benign ★★ 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-gln424pro (accessed [today's date]).

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