Is HGF p.Ser331Phe (c.992C>T) pathogenic?

HGF p.Ser331Phe (c.992C>T) is classified Uncertain significance in HGF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-10). AlphaMissense: likely benign (0.2135); Absent from gnomAD v4.1.

How common is HGF p.Ser331Phe (c.992C>T) in the general population?

HGF p.Ser331Phe (c.992C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about HGF p.Ser331Phe (c.992C>T)?

AlphaMissense predicts likely benign (score 0.2135) — an in-silico prediction, not a clinical call.

HGF p.Ser331Phe

c.992C>T · VCV3390701

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2135 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2135	likely benign
REVEL	0.523	indeterminate
SaProt	LLR -11.21	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 64 kb · p 4.1e-07 · regional, not allelic
Overall
CADD	28.7	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

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: HGF
Protein: p.Ser331Phe
Coding: c.992C>T
MANE Select: NM_000601
Type: single nucleotide variant
Location: chr7:81729653 (GRCh38)
Gene constraint: LOEUF 0.471 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 36 PDB
Residue 331: the kringle 3 domain

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-ser331phe (accessed [today's date]).

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