Is MEFV p.Leu10= (c.30G>A) pathogenic?

MEFV p.Leu10= (c.30G>A) is classified Likely benign in MEFV (ClinVar, Single submitter, 2 submitters; last evaluated 2025-08-18). Very rare (popmax 0.00266%, afr); Associated with familial Mediterranean fever.

What condition is associated with MEFV p.Leu10= (c.30G>A)?

MEFV p.Leu10= (c.30G>A) is associated with familial Mediterranean fever (ClinVar).

How common is MEFV p.Leu10= (c.30G>A) in the general population?

MEFV p.Leu10= (c.30G>A) is very rare (popmax 0.00266%, afr) (gnomAD).

How is Familial Mediterranean fever inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

MEFV p.Leu10=

c.30G>A · rs553819712 · VCV990370

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00266%, afr)

Conditions

familial Mediterranean fever

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 -1.3	GERP -4.2
Overall
CADD	7.259	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00266% African / African-American · 2/75,058 alleles

Filtering AF 0.000442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000248% 4/1,614,212 alleles · very rare exomes 2/1,461,880 · genomes 2/152,332 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00266%	37,529
Remaining individualsnot grpmax-eligible	0.0016%	62,508
South Asian	0.0011%	91,088

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.Leu10=
Coding: c.30G>A
MANE Select: NM_000243
dbSNP: rs553819712
Type: single nucleotide variant
Location: chr16:3256558 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 73.64 · 11 PDB
Residue 10: the pyrin domain; an α-helix

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

Disease context

familial Mediterranean fever — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial Mediterranean fever (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy
Prevalence: >1 / 1000 (Turkey)

Similar variants

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
MEFV p.Ala416Thr Uncertain significance ★★ ⚠ same condition
MEFV p.Ala768Gly 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-leu10 (accessed [today's date]).

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