Is CHML p.His337Arg (c.1010A>G) pathogenic?

CHML p.His337Arg (c.1010A>G) is classified Uncertain significance in CHML (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-20). AlphaMissense: likely benign (0.184); Rare (popmax 0.127%, afr).

How common is CHML p.His337Arg (c.1010A>G) in the general population?

CHML p.His337Arg (c.1010A>G) is rare (popmax 0.127%, afr) (gnomAD).

What do computational predictors say about CHML p.His337Arg (c.1010A>G)?

AlphaMissense predicts likely benign (score 0.184) — an in-silico prediction, not a clinical call.

CHML p.His337Arg

c.1010A>G · rs148647394 · VCV3144410

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.184 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.127%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.184	likely benign
REVEL	0.71	pathogenic-leaning
SaProt	LLR -11.04	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.9	GERP 2, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 1,967 bp · p 0.34 · regional, not allelic
Overall
CADD	24.6	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 0.127% African / African-American · 95/74,920 alleles

Filtering AF 0.106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0984%

Overall 0.00725% 117/1,613,884 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.127%	789
Remaining individualsnot grpmax-eligible	0.0192%	5,206
Admixed American	0.015%	6,667
European (non-Finnish)	8.48e-05%	1,179,898

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: CHML
Protein: p.His337Arg
Coding: c.1010A>G
MANE Select: NM_014322 · reported on NM_001381853
dbSNP: rs148647394
Type: single nucleotide variant
Location: chr1:241634757 (GRCh38)

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

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/chml-p-his337arg (accessed [today's date]).

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