Is HGF p.Pro267= (c.801G>C) pathogenic?

HGF p.Pro267= (c.801G>C) is classified Likely benign in HGF (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-03). Very rare (popmax 0.00333%, amr).

How common is HGF p.Pro267= (c.801G>C) in the general population?

HGF p.Pro267= (c.801G>C) is very rare (popmax 0.00333%, amr) (gnomAD).

HGF p.Pro267=

c.801G>C · rs1788088901 · VCV2781654

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

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 1.8	GERP 2.2, phastCons 1
Overall
CADD	11.76	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/59,992 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000124% 2/1,613,734 alleles · very rare exomes 0/1,461,640 · genomes 2/152,094 · joint denominator

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: HGF
Protein: p.Pro267=
Coding: c.801G>C
MANE Select: NM_000601
dbSNP: rs1788088901
Type: single nucleotide variant
Location: chr7:81743417 (GRCh38)
Gene constraint: LOEUF 0.471 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.76 · 36 PDB
Residue 267: the kringle 2 domain

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

Similar variants

HGF p.Pro267Leu Uncertain significance ★ ⚠ same residue
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

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-pro267 (accessed [today's date]).

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