Is GHITM p.Val91Ile (c.271G>A) pathogenic?

GHITM p.Val91Ile (c.271G>A) is classified Uncertain significance in GHITM (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-05). AlphaMissense: likely benign (0.0871); Very rare (popmax 0.00669%, eas).

How common is GHITM p.Val91Ile (c.271G>A) in the general population?

GHITM p.Val91Ile (c.271G>A) is very rare (popmax 0.00669%, eas) (gnomAD).

What do computational predictors say about GHITM p.Val91Ile (c.271G>A)?

AlphaMissense predicts likely benign (score 0.0871) — an in-silico prediction, not a clinical call.

GHITM p.Val91Ile

c.271G>A · rs370349475 · VCV3099724

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0871 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0871	likely benign
REVEL	0.293	indeterminate
SaProt	LLR -7.64	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP 5, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 11 kb · p 0.64 · regional, not allelic
Overall
CADD	23.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00669% East Asian · 3/44,870 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000496% 8/1,614,136 alleles · very rare exomes 7/1,461,796 · genomes 1/152,340 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,957
Remaining individualsnot grpmax-eligible	0.0048%	20,835
Admixed American	0.00167%	60,034
South Asian	0.0011%	91,092

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: GHITM
Protein: p.Val91Ile
Coding: c.271G>A
MANE Select: NM_014394
dbSNP: rs370349475
Type: single nucleotide variant
Location: chr10:84144036 (GRCh38)
Gene constraint: LOEUF 0.965 · pLI 0.51 (gnomAD)
Structure: AlphaFold pLDDT 77.05

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

Similar variants

GHITM p.Met129Val Uncertain significance ★★ ⚠ same type
GHITM p.Ala109Gly Uncertain significance ★ same type
GHITM p.Ala113Ser Uncertain significance ★ ⚠ same type
GHITM p.Ala144Thr Uncertain significance ★ ⚠ same type
GHITM p.Ala279Ser Uncertain significance ★ ⚠ same type
GHITM p.Ala279Val Uncertain significance ★ ⚠ same type
GHITM p.Ala302Glu Uncertain significance ★ ⚠ same type
GHITM p.Arg10Trp 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/ghitm-p-val91ile (accessed [today's date]).

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