Is CHM p.His122Arg (c.365A>G) pathogenic?

CHM p.His122Arg (c.365A>G) is classified Conflicting classifications of pathogenicity in CHM (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-09-29). AlphaMissense: likely benign (0.0652); Ultra-rare (popmax 0.0237%, eas); Associated with Inborn genetic diseases.

What condition is associated with CHM p.His122Arg (c.365A>G)?

CHM p.His122Arg (c.365A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CHM p.His122Arg (c.365A>G) in the general population?

CHM p.His122Arg (c.365A>G) is ultra-rare (popmax 0.0237%, eas) (gnomAD).

What do computational predictors say about CHM p.His122Arg (c.365A>G)?

AlphaMissense predicts likely benign (score 0.0652) — an in-silico prediction, not a clinical call.

CHM p.His122Arg

c.365A>G · rs765999807 · VCV2281102

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0652 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0237%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0652	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -6.55	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.89	GERP -5.7, phastCons 0.77
Regional constraint	o/e 0.95	unconstrained · MANE · 183 kb · p 0.28 · regional, not allelic
Overall
CADD	10.47	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 · 8/33,709 alleles

Filtering AF 0.0118% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00852%

Overall 0.000911% 11/1,206,926 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0237%	4,214
Remaining individualsnot grpmax-eligible	0.00421%	23,756
European (non-Finnish)	0.000112%	894,118

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.His122Arg
Coding: c.365A>G
MANE Select: NM_000390
dbSNP: rs765999807
Type: single nucleotide variant
Location: chrX:85964002 (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.His122Asn Uncertain significance ★ ⚠ 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
CHM p.Asn610Asp Uncertain significance ★★ ⚠ same condition
CHM p.Asp280His 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-his122arg (accessed [today's date]).

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