Is FAS p.Gln47= (c.141G>A) pathogenic?

FAS p.Gln47= (c.141G>A) is classified Benign in FAS (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-01). Common (popmax 6.94%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Meniere disease.

What condition is associated with FAS p.Gln47= (c.141G>A)?

FAS p.Gln47= (c.141G>A) is associated with Meniere disease, autoimmune lymphoproliferative syndrome type 1 (ClinVar).

FAS p.Gln47=

Q: How common is FAS p.Gln47= (c.141G>A) in the general population?

FAS p.Gln47= (c.141G>A) is common (popmax 6.94%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.141G>A · rs3218621 · VCV301525

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 6.94%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Meniere disease

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 -0.13	GERP -2.8
Overall
CADD	0.503	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.94% African / African-American · 5,207/75,030 alleles

Filtering AF 6.78% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.72%

Overall 0.375% 6,050/1,614,160 alleles · common exomes 3,001/1,461,850 · genomes 3,049/152,310 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.94%	14
Remaining individualsnot grpmax-eligible	0.515%	194
Admixed American	0.428%	234
Middle Eastern	0.247%	404
European (non-Finnish)	0.0197%	5,064
South Asian	0.0176%	5,693

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: FAS
Protein: p.Gln47=
Coding: c.141G>A
MANE Select: NM_000043
dbSNP: rs3218621
Type: single nucleotide variant
Location: chr10:89003139 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 78.21 · 7 PDB

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

Disease context

Meniere disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autoimmune lymphoproliferative syndrome type 1

Similar variants

FAS p.Gln47Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
FAS c.651+1G>A Pathogenic/Likely pathogenic ★★ same condition
FAS c.651+2T>C Pathogenic ★★ same condition
FAS p.Arg250Gln Pathogenic/Likely pathogenic ★★ same condition
FAS p.Arg250Gly Likely pathogenic ★★ same condition
FAS p.Arg250Ter Pathogenic/Likely pathogenic ★★ same condition
FAS p.Asp260Asn Pathogenic ★★ ⚠ same condition
FAS p.Cys135Tyr Likely pathogenic ★★ 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/fas-p-gln47 (accessed [today's date]).

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