Is CHM p.Arg414Gly (c.1240A>G) pathogenic?

CHM p.Arg414Gly (c.1240A>G) is classified Uncertain significance in CHM (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-17). AlphaMissense: likely benign (0.046); Very rare (popmax 0.000582%, nfe).

How common is CHM p.Arg414Gly (c.1240A>G) in the general population?

CHM p.Arg414Gly (c.1240A>G) is very rare (popmax 0.000582%, nfe) (gnomAD).

What do computational predictors say about CHM p.Arg414Gly (c.1240A>G)?

AlphaMissense predicts likely benign (score 0.046) — an in-silico prediction, not a clinical call.

CHM p.Arg414Gly

c.1240A>G · rs1927009078 · VCV1384060

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.046 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000582%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.046	likely benign
REVEL	0.227	benign-leaning
SaProt	LLR -6.07	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 -2.5	GERP -1.9
Regional constraint	o/e 0.95	unconstrained · MANE · 183 kb · p 0.28 · regional, not allelic
Overall
CADD	5.379	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 0.000582% European (non-Finnish) · 4/686,907 alleles

Filtering AF 0.000136% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.2e-05%

Overall 0.00049% 4/816,816 alleles · very rare

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.Arg414Gly
Coding: c.1240A>G
MANE Select: NM_000390
dbSNP: rs1927009078
Type: single nucleotide variant
Location: chrX:85911265 (GRCh38)
Structure: AlphaFold pLDDT 81.05

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

Similar variants

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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-arg414gly (accessed [today's date]).

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