Is CHM p.Arg367Trp (c.1099C>T) pathogenic?

CHM p.Arg367Trp (c.1099C>T) is classified Conflicting classifications of pathogenicity in CHM (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-05-07). AlphaMissense: ambiguous (0.362); Ultra-rare (popmax 0.0237%, eas); Associated with Inborn genetic diseases.

What condition is associated with CHM p.Arg367Trp (c.1099C>T)?

CHM p.Arg367Trp (c.1099C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CHM p.Arg367Trp (c.1099C>T) in the general population?

CHM p.Arg367Trp (c.1099C>T) is ultra-rare (popmax 0.0237%, eas) (gnomAD).

What do computational predictors say about CHM p.Arg367Trp (c.1099C>T)?

AlphaMissense predicts ambiguous (score 0.362) — an in-silico prediction, not a clinical call.

CHM p.Arg367Trp

c.1099C>T · rs760000110 · VCV1079569

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.362 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0237%, eas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.362	ambiguous
REVEL	0.925	moderately pathogenic-leaning
SaProt	LLR -15.95	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 2.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 183 kb · p 0.28 · regional, not allelic
Overall
CADD	25.5	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 0.0237% East Asian · 8/33,738 alleles

Filtering AF 0.0117% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00852%

Overall 0.00165% 20/1,209,096 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0237%	4,217
Remaining individualsnot grpmax-eligible	0.0042%	23,787
African / African-American	0.00351%	28,497
Admixed American	0.00219%	45,596
South Asian	0.00176%	56,743
European (non-Finnish)	0.00067%	149,150

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.Arg367Trp
Coding: c.1099C>T
MANE Select: NM_000390
dbSNP: rs760000110
Type: single nucleotide variant
Location: chrX:85956220 (GRCh38)
Structure: AlphaFold pLDDT 81.05

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHM p.Arg367Gln Benign/Likely benign ★★ ⚠ same residue
CHM p.Arg367Leu Benign/Likely benign ★★ same residue
CHM p.Arg367= Likely benign ★ same residue
CHM p.Ala123Val Uncertain significance ★★ ⚠ same condition
CHM p.Ala133Thr Uncertain significance ★★ ⚠ same condition
CHM p.Ala166Glu Uncertain significance ★★ ⚠ same condition
CHM p.Arg555Thr Uncertain significance ★★ ⚠ same condition
CHM p.Asn553Asp Uncertain significance ★★ ⚠ same condition

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-arg367trp (accessed [today's date]).

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