Is MEFV p.Arg151Thr (c.452G>C) pathogenic?

MEFV p.Arg151Thr (c.452G>C) is classified Uncertain significance in MEFV (ClinVar, Single submitter, 1 submitter; last evaluated 2016-01-29). AlphaMissense: likely benign (0.1371); Very rare (popmax 0.000425%, nfe).

How common is MEFV p.Arg151Thr (c.452G>C) in the general population?

MEFV p.Arg151Thr (c.452G>C) is very rare (popmax 0.000425%, nfe) (gnomAD).

What do computational predictors say about MEFV p.Arg151Thr (c.452G>C)?

AlphaMissense predicts likely benign (score 0.1371) — an in-silico prediction, not a clinical call.

MEFV p.Arg151Thr

c.452G>C · rs886043273 · VCV285970

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1371 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000425%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1371	likely benign
REVEL	0.151	moderately benign-leaning
SaProt	LLR -6.47	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 -1.9	GERP -4.1
Regional constraint	o/e 1.16	unconstrained · MANE · 13 kb · p 2.1e-07 · regional, not allelic
Overall
CADD	5.935	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 0.000425% European (non-Finnish) · 5/1,177,030 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000312% 5/1,603,456 alleles · very rare exomes 5/1,451,098 · genomes 0/152,358 · 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.Arg151Thr
Coding: c.452G>C
MANE Select: NM_000243
dbSNP: rs886043273
Type: single nucleotide variant
Location: chr16:3254616 (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

Similar variants

MEFV p.Arg151Ser Uncertain significance ★★ ⚠ same residue
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.Arg761His Pathogenic/Likely pathogenic ★★ ⚠ same type
MEFV p.Ser242Arg Pathogenic/Likely pathogenic ★★ same type
MEFV p.Val726Ala Pathogenic/Likely pathogenic ★★ ⚠ same type

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-arg151thr (accessed [today's date]).

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