Is CHM p.Arg401His (c.1202G>A) pathogenic?

CHM p.Arg401His (c.1202G>A) is classified Uncertain significance in CHM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-13). AlphaMissense: likely benign (0.1054); Very rare (popmax 0.00373%, sas).

How common is CHM p.Arg401His (c.1202G>A) in the general population?

CHM p.Arg401His (c.1202G>A) is very rare (popmax 0.00373%, sas) (gnomAD).

What do computational predictors say about CHM p.Arg401His (c.1202G>A)?

AlphaMissense predicts likely benign (score 0.1054) — an in-silico prediction, not a clinical call.

CHM p.Arg401His

c.1202G>A · rs1927014512 · VCV2198517

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1054 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00373%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1054	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -11.42	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP 0.094, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 183 kb · p 0.28 · regional, not allelic
Overall
CADD	23.0	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 0.00373% South Asian · 2/53,548 alleles

Filtering AF 0.000619% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000232%

Overall 0.000832% 8/961,945 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00373%	26,774
European (non-Finnish)	0.000755%	132,451

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.Arg401His
Coding: c.1202G>A
MANE Select: NM_000390
dbSNP: rs1927014512
Type: single nucleotide variant
Location: chrX:85911303 (GRCh38)
Structure: AlphaFold pLDDT 81.05

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

Similar variants

CHM p.Arg401Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
CHM p.Arg401= Likely benign ★ 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-arg401his (accessed [today's date]).

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