Is MEFV p.Asp510= (c.1530T>C) pathogenic?

MEFV p.Asp510= (c.1530T>C) is classified Benign/Likely benign in MEFV (ClinVar, Multiple submitters, 16 submitters; last evaluated 2026-02-04). Common (popmax 71.5%, sas) — too common for a highly-penetrant pathogenic allele; Associated with autoinflammatory syndrome.

What condition is associated with MEFV p.Asp510= (c.1530T>C)?

MEFV p.Asp510= (c.1530T>C) is associated with autoinflammatory syndrome, familial Mediterranean fever, autosomal dominant, familial Mediterranean fever (ClinVar).

MEFV p.Asp510=

Q: How common is MEFV p.Asp510= (c.1530T>C) in the general population?

MEFV p.Asp510= (c.1530T>C) is common (popmax 71.5%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1530T>C · rs224206 · VCV36503

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 16 submitters

gnomAD v4.1

Common

common (popmax 71.5%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

autoinflammatory syndrome

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 -5.9	GERP -4
Overall
CADD	0.074	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 71.5% South Asian · 65,096/91,088 alleles

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

Overall 57% 920,721/1,613,894 alleles · common exomes 829,639/1,461,850 · genomes 91,082/152,044 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	71.5%	1
Admixed American	70.3%	1
African / African-American	68.8%	1
East Asian	63.9%	2
Remaining individualsnot grpmax-eligible	57.5%	2
Finnishnot grpmax-eligible	56.2%	2
Middle Eastern	55.9%	2
Ashkenazi Jewishnot grpmax-eligible	55.1%	2
European (non-Finnish)	54.3%	2
Amishnot grpmax-eligible	40.2%	2

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.Asp510=
Coding: c.1530T>C
MANE Select: NM_000243
dbSNP: rs224206
Type: single nucleotide variant
Location: chr16:3247073 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 73.64 · 11 PDB
Residue 510: 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

autoinflammatory syndrome — 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.Asp510Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
MEFV p.Asp510Glu 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-asp510 (accessed [today's date]).

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