Is CHM p.Ile341Val (c.1021A>G) pathogenic?

CHM p.Ile341Val (c.1021A>G) is classified Uncertain significance in CHM (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-03). AlphaMissense: likely benign (0.1296); Very rare (popmax 0.00652%, amr).

How common is CHM p.Ile341Val (c.1021A>G) in the general population?

CHM p.Ile341Val (c.1021A>G) is very rare (popmax 0.00652%, amr) (gnomAD).

What do computational predictors say about CHM p.Ile341Val (c.1021A>G)?

AlphaMissense predicts likely benign (score 0.1296) — an in-silico prediction, not a clinical call.

CHM p.Ile341Val

c.1021A>G · rs766977263 · VCV1522323

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1296 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00652%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1296	likely benign
REVEL	0.482	indeterminate
SaProt	LLR -8.25	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.35	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 5.9	GERP 2.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 183 kb · p 0.28 · regional, not allelic
Overall
CADD	25.6	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

Grpmax group 0.00652% Admixed American · 3/46,016 alleles

Filtering AF 0.00173% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000879%

Overall 0.000547% 6/1,097,808 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00652%	15,339
European (non-Finnish)	0.000335%	298,425

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.Ile341Val
Coding: c.1021A>G
MANE Select: NM_000390
dbSNP: rs766977263
Type: single nucleotide variant
Location: chrX:85956298 (GRCh38)
Structure: AlphaFold pLDDT 81.05

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

Similar variants

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
CHM c.1244+2T>A Pathogenic/Likely pathogenic ★★ same type
CHM c.1349+1G>T Pathogenic/Likely 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-ile341val (accessed [today's date]).

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