Is FHIT p.Val97Ile (c.289G>A) pathogenic?

FHIT p.Val97Ile (c.289G>A) is classified Likely benign in FHIT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-09). AlphaMissense: likely benign (0.0869); Ultra-rare (popmax 0.0253%, afr).

How common is FHIT p.Val97Ile (c.289G>A) in the general population?

FHIT p.Val97Ile (c.289G>A) is ultra-rare (popmax 0.0253%, afr) (gnomAD).

What do computational predictors say about FHIT p.Val97Ile (c.289G>A)?

AlphaMissense predicts likely benign (score 0.0869) — an in-silico prediction, not a clinical call.

FHIT p.Val97Ile

c.289G>A · VCV4024969

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0869 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0253%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0869	likely benign
REVEL	0.229	benign-leaning
SaProt	LLR -7.29	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.036	GERP -4.3, phastCons 0.001
Regional constraint	o/e 1.31	unconstrained · MANE · 785 kb · p 1.9e-05 · regional, not allelic
Overall
CADD	6.492	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0253% African / African-American · 19/74,972 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0137%

Overall 0.00521% 84/1,613,354 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0253%	3,946
South Asian	0.0121%	8,275
European (non-Finnish)	0.00441%	22,685
East Asian	0.00223%	44,860
Remaining individualsnot grpmax-eligible	0.0016%	62,494

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: FHIT
Protein: p.Val97Ile
Coding: c.289G>A
MANE Select: NM_002012
Type: single nucleotide variant
Location: chr3:59922405 (GRCh38)
Gene constraint: LOEUF 1.57 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 95.15 · 9 PDB
Residue 97: the hit domain; a β-strand

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

Similar variants

FHIT p.Ala127Asp Uncertain significance ★ ⚠ same type
FHIT p.Ala141Ser Uncertain significance ★ ⚠ same type
FHIT p.Ala24Pro Uncertain significance ★ ⚠ same type
FHIT p.Arg46Cys Uncertain significance ★ ⚠ same type
FHIT p.Arg46His Uncertain significance ★ ⚠ same type
FHIT p.Arg51His Uncertain significance ★ ⚠ same type
FHIT p.Asn110Ser Uncertain significance ★ ⚠ same type
FHIT p.Cys39Tyr Uncertain significance ★ ⚠ same type

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/fhit-p-val97ile (accessed [today's date]).

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