Is MEFV p.Gln476= (c.1428A>G) pathogenic?

MEFV p.Gln476= (c.1428A>G) is classified Benign/Likely benign in MEFV (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-02-04). Common (popmax 71.4%, sas) — too common for a highly-penetrant pathogenic allele; Associated with Inborn genetic diseases.

What condition is associated with MEFV p.Gln476= (c.1428A>G)?

MEFV p.Gln476= (c.1428A>G) is associated with Inborn genetic diseases, familial Mediterranean fever, autosomal dominant, familial Mediterranean fever (ClinVar).

MEFV p.Gln476=

Q: How common is MEFV p.Gln476= (c.1428A>G) in the general population?

MEFV p.Gln476= (c.1428A>G) is common (popmax 71.4%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1428A>G · rs224207 · VCV255615

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

gnomAD v4.1

Common

common (popmax 71.4%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.97	GERP -4, phastCons 0.004
Overall
CADD	0.822	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 71.4% South Asian · 65,055/91,064 alleles

Filtering AF 71% ClinGen BA1/BS1 input FAF95, joint · FAF99 70.8%

Overall 56.7% 914,332/1,613,124 alleles · common exomes 825,635/1,461,544 · genomes 88,697/151,580 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	71.4%	1
Admixed American	69.9%	1
African / African-American	64.5%	2
East Asian	63.9%	2
Remaining individualsnot grpmax-eligible	57.1%	2
Finnishnot grpmax-eligible	56.1%	2
Middle Eastern	55.2%	2
Ashkenazi Jewishnot grpmax-eligible	55.1%	2
European (non-Finnish)	54.2%	2
Amishnot grpmax-eligible	39.8%	3

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.Gln476=
Coding: c.1428A>G
MANE Select: NM_000243
dbSNP: rs224207
Type: single nucleotide variant
Location: chr16:3247175 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 73.64 · 11 PDB
Residue 476: 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

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

Similar variants

MEFV p.Gln476Glu Uncertain significance ★ ⚠ same residue
MEFV p.Gln476His 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
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-gln476 (accessed [today's date]).

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