Is HGF p.Ile26Val (c.76A>G) pathogenic?

HGF p.Ile26Val (c.76A>G) is classified Uncertain significance in HGF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-02). AlphaMissense: likely benign (0.0708); No allele count reported in gnomAD v4.1 (AN 1,566,400).

How common is HGF p.Ile26Val (c.76A>G) in the general population?

HGF p.Ile26Val (c.76A>G) is no allele count reported in gnomAD v4.1 (AN 1,566,400) (gnomAD).

What do computational predictors say about HGF p.Ile26Val (c.76A>G)?

AlphaMissense predicts likely benign (score 0.0708) — an in-silico prediction, not a clinical call.

HGF p.Ile26Val

c.76A>G · VCV3776406

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0708 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,566,400)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0708	likely benign
REVEL	0.07	moderately benign-leaning
SaProt	LLR -5.71	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 1.5	GERP 0.27, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 64 kb · p 4.1e-07 · regional, not allelic
Overall
CADD	12.76	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

No allele count reported in gnomAD v4.1 (AN 1,566,400). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: HGF
Protein: p.Ile26Val
Coding: c.76A>G
MANE Select: NM_000601
Type: single nucleotide variant
Location: chr7:81769896 (GRCh38)
Gene constraint: LOEUF 0.471 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 36 PDB

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

Similar variants

HGF p.Ala432Val Uncertain significance ★★ ⚠ same type
HGF p.Ala661Thr Uncertain significance ★★ ⚠ same type
HGF p.Arg168Trp Uncertain significance ★★ ⚠ same type
HGF p.Arg220Gln Uncertain significance ★★ ⚠ same type
HGF p.Arg242Gln Uncertain significance ★★ ⚠ same type
HGF p.Arg242Trp Uncertain significance ★★ ⚠ same type
HGF p.Arg328His Uncertain significance ★★ ⚠ same type
HGF p.Arg350Gln 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/hgf-p-ile26val (accessed [today's date]).

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