Is MEFV p.Gln753= (c.2259A>G) pathogenic?

MEFV p.Gln753= (c.2259A>G) is classified Likely benign in MEFV (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-06). Very rare (popmax 0.0022%, sas); Associated with Inborn genetic diseases.

What condition is associated with MEFV p.Gln753= (c.2259A>G)?

MEFV p.Gln753= (c.2259A>G) is associated with Inborn genetic diseases, familial Mediterranean fever (ClinVar).

How common is MEFV p.Gln753= (c.2259A>G) in the general population?

MEFV p.Gln753= (c.2259A>G) is very rare (popmax 0.0022%, sas) (gnomAD).

MEFV p.Gln753=

c.2259A>G · rs104895174 · VCV97506

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

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 -0.19	GERP -2.7, phastCons 0.4
Overall
CADD	0.889	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,082 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.00031% 5/1,614,092 alleles · very rare exomes 5/1,461,868 · genomes 0/152,224 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,541
African / African-American	0.00133%	75,016
European (non-Finnish)	0.000169%	590,016

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.Gln753=
Coding: c.2259A>G
MANE Select: NM_000243
dbSNP: rs104895174
Type: single nucleotide variant
Location: chr16:3243228 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 73.64 · 11 PDB
Residue 753: a β-strand; the b30.2/spry domain

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

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-gln753 (accessed [today's date]).

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