Is MEFV p.Asp391= (c.1173T>C) pathogenic?

MEFV p.Asp391= (c.1173T>C) is classified Conflicting classifications of pathogenicity in MEFV (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-20). Ultra-rare (popmax 0.0165%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MEFV p.Asp391= (c.1173T>C)?

MEFV p.Asp391= (c.1173T>C) is associated with Inborn genetic diseases, familial Mediterranean fever (ClinVar).

How common is MEFV p.Asp391= (c.1173T>C) in the general population?

MEFV p.Asp391= (c.1173T>C) is ultra-rare (popmax 0.0165%, nfe) (gnomAD).

MEFV p.Asp391=

c.1173T>C · rs146077729 · VCV319114

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.2	GERP -1.1
Overall
CADD	2.216	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% European (non-Finnish) · 195/1,180,042 alleles

Filtering AF 0.0146% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0139%

Overall 0.0996% 1,608/1,614,214 alleles · ultra-rare exomes 1,316/1,461,866 · genomes 292/152,348 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	2.13%	47
Remaining individualsnot grpmax-eligible	0.072%	1,389
European (non-Finnish)grpmax	0.0165%	6,052
South Asian	0.0011%	91,084

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp391=
Coding: c.1173T>C
MANE Select: NM_000243
dbSNP: rs146077729
Type: single nucleotide variant
Location: chr16:3249518 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 73.64 · 11 PDB

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.Asp391Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
MEFV p.Asp391Glu 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-asp391 (accessed [today's date]).

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