Is CHM p.Val447Met (c.1339G>A) pathogenic?

CHM p.Val447Met (c.1339G>A) is classified Benign/Likely benign in CHM (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-03). AlphaMissense: likely benign (0.1385); Ultra-rare (popmax 0.0457%, afr).

How common is CHM p.Val447Met (c.1339G>A) in the general population?

CHM p.Val447Met (c.1339G>A) is ultra-rare (popmax 0.0457%, afr) (gnomAD).

What do computational predictors say about CHM p.Val447Met (c.1339G>A)?

AlphaMissense predicts likely benign (score 0.1385) — an in-silico prediction, not a clinical call.

CHM p.Val447Met

c.1339G>A · rs142989054 · VCV1628505

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1385 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0457%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1385	likely benign
REVEL	0.386	indeterminate
SaProt	LLR -5.67	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP 0.25, phastCons 0.94
Regional constraint	o/e 0.95	unconstrained · MANE · 183 kb · p 0.28 · regional, not allelic
Overall
CADD	20.4	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 0.0457% African / African-American · 26/56,836 alleles

Filtering AF 0.032% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0274%

Overall 0.00234% 28/1,195,045 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0457%	2,186
Remaining individualsnot grpmax-eligible	0.00425%	23,556

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: CHM
Protein: p.Val447Met
Coding: c.1339G>A
MANE Select: NM_000390
dbSNP: rs142989054
Type: single nucleotide variant
Location: chrX:85901094 (GRCh38)
Structure: AlphaFold pLDDT 81.05

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

Similar variants

CHM p.Val447= Likely benign ★ same residue
CHM p.Val447fs Pathogenic ★ same residue
CHM c.116+1G>A Pathogenic/Likely pathogenic ★★ same type
CHM c.116+1G>T Pathogenic/Likely pathogenic ★★ same type
CHM c.1166+1G>A Pathogenic ★★ same type
CHM c.1166+1G>C Pathogenic ★★ same type
CHM c.1167-2A>G Pathogenic ★★ same type
CHM c.1244+1G>A Pathogenic ★★ 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/chm-p-val447met (accessed [today's date]).

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