Is CHM p.Arg367Leu (c.1100G>T) pathogenic?

CHM p.Arg367Leu (c.1100G>T) is classified Benign/Likely benign in CHM (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-05). AlphaMissense: likely pathogenic (0.6266); Rare (popmax 0.369%, sas).

How common is CHM p.Arg367Leu (c.1100G>T) in the general population?

CHM p.Arg367Leu (c.1100G>T) is rare (popmax 0.369%, sas) (gnomAD).

What do computational predictors say about CHM p.Arg367Leu (c.1100G>T)?

AlphaMissense predicts likely pathogenic (score 0.6266) — an in-silico prediction, not a clinical call.

CHM p.Arg367Leu

c.1100G>T · rs76191025 · VCV286771

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.6266 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.369%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6266	likely pathogenic
REVEL	0.91	moderately pathogenic-leaning
SaProt	LLR -12.86	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP 2.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 183 kb · p 0.28 · regional, not allelic
Overall
CADD	24.7	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 0.369% South Asian · 209/56,607 alleles

Filtering AF 0.328% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.312%

Overall 0.0205% 248/1,208,874 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.369%	271
Remaining individualsnot grpmax-eligible	0.021%	4,760
European (non-Finnish)	0.00302%	33,141
Admixed American	0.00219%	45,601
Finnishnot grpmax-eligible	0.00215%	46,433

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.Arg367Leu
Coding: c.1100G>T
MANE Select: NM_000390
dbSNP: rs76191025
Type: single nucleotide variant
Location: chrX:85956219 (GRCh38)
Structure: AlphaFold pLDDT 81.05

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

Similar variants

CHM p.Arg367Gln Benign/Likely benign ★★ ⚠ same residue
CHM p.Arg367Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
CHM p.Arg367= Likely benign ★ same residue
CHM p.Arg367fs 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

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-arg367leu (accessed [today's date]).

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