Is MEFV p.Asn99= (c.297C>T) pathogenic?

MEFV p.Asn99= (c.297C>T) is classified Conflicting classifications of pathogenicity in MEFV (ClinVar, Conflicting submitters, 11 submitters; last evaluated 2026-01-29). Very rare (popmax 0.00492%, nfe); Associated with autoinflammatory syndrome.

What condition is associated with MEFV p.Asn99= (c.297C>T)?

MEFV p.Asn99= (c.297C>T) is associated with autoinflammatory syndrome, familial Mediterranean fever, autosomal dominant, familial Mediterranean fever (ClinVar).

How common is MEFV p.Asn99= (c.297C>T) in the general population?

MEFV p.Asn99= (c.297C>T) is very rare (popmax 0.00492%, nfe) (gnomAD).

MEFV p.Asn99=

c.297C>T · rs104895175 · VCV97514

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 11 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00492%, nfe)

Conditions

autoinflammatory syndrome

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 -0.18	GERP -4.1
Overall
CADD	0.782	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00492% European (non-Finnish) · 58/1,180,028 alleles

Filtering AF 0.00386% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00353%

Overall 0.0254% 410/1,612,066 alleles · very rare exomes 363/1,459,814 · genomes 47/152,252 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.02%	98
Remaining individualsnot grpmax-eligible	0.0784%	1,275
European (non-Finnish)grpmax	0.00492%	20,345
Admixed American	0.00167%	60,012
African / African-American	0.00133%	74,946

Ashkenazi Jewish 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.Asn99=
Coding: c.297C>T
MANE Select: NM_000243
dbSNP: rs104895175
Type: single nucleotide variant
Location: chr16:3254771 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 73.64 · 11 PDB
Residue 99: the 'disordered' 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.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.Ala744Thr 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-asn99 (accessed [today's date]).

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