Is MEFV p.Glu85Val (c.254A>T) pathogenic?

MEFV p.Glu85Val (c.254A>T) is classified Uncertain significance in MEFV (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-17). AlphaMissense: ambiguous (0.5438); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MEFV p.Glu85Val (c.254A>T)?

MEFV p.Glu85Val (c.254A>T) is associated with Inborn genetic diseases (ClinVar).

How common is MEFV p.Glu85Val (c.254A>T) in the general population?

MEFV p.Glu85Val (c.254A>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about MEFV p.Glu85Val (c.254A>T)?

AlphaMissense predicts ambiguous (score 0.5438) — an in-silico prediction, not a clinical call.

MEFV p.Glu85Val

c.254A>T · rs2543159348 · VCV3230738

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5438 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5438	ambiguous
REVEL	0.428	indeterminate
SaProt	LLR -9.12	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 2.1, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 13 kb · p 2.1e-07 · regional, not allelic
Overall
CADD	24.3	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 8.47e-05% European (non-Finnish) · 1/1,179,988 alleles

Overall 6.2e-05% 1/1,613,884 alleles · very rare exomes 1/1,461,572 · genomes 0/152,312 · joint denominator

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.Glu85Val
Coding: c.254A>T
MANE Select: NM_000243
dbSNP: rs2543159348
Type: single nucleotide variant
Location: chr16:3256334 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 73.64 · 11 PDB
Residue 85: the pyrin domain; an α-helix

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.Glu85Lys Uncertain significance ★ ⚠ same residue
MEFV p.Glu85= Likely benign ★ same residue
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

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-glu85val (accessed [today's date]).

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