Is FH p.Ala332= (c.996C>G) pathogenic?

FH p.Ala332= (c.996C>G) is classified Likely benign in FH (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-06). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with FH p.Ala332= (c.996C>G)?

FH p.Ala332= (c.996C>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is FH p.Ala332= (c.996C>G) in the general population?

FH p.Ala332= (c.996C>G) is absent from gnomAD v4.1 (gnomAD).

FH p.Ala332=

c.996C>G · rs2527319513 · VCV1768757

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic 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 -1.2	GERP -5.6
Overall
CADD	1.451	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FH
Protein: p.Ala332=
Coding: c.996C>G
MANE Select: NM_000143
dbSNP: rs2527319513
Type: single nucleotide variant
Location: chr1:241504154 (GRCh38)
Gene constraint: LOEUF 0.599 · pLI 0.27 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 92.92 · 8 PDB
Residue 332: an α-helix

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FH p.Ala332Thr Uncertain significance ★★ ⚠ same residue
FH p.Ala332Pro Likely pathogenic ★ same residue
FH p.Ala332Val Uncertain significance ★ ⚠ same residue
FH c.1108+1G>T Pathogenic/Likely pathogenic ★★ same condition
FH c.1236+1G>A Pathogenic/Likely pathogenic ★★ same condition
FH c.1236+1G>C Pathogenic ★★ same condition
FH c.1236+2T>G Pathogenic ★★ same condition
FH c.1237-1G>T 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/fh-p-ala332 (accessed [today's date]).

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