Is CHM p.Gln448Arg (c.1343A>G) pathogenic?

CHM p.Gln448Arg (c.1343A>G) is classified Uncertain significance in CHM (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-01). AlphaMissense: likely benign (0.0755); Absent from gnomAD v4.1.

How common is CHM p.Gln448Arg (c.1343A>G) in the general population?

CHM p.Gln448Arg (c.1343A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHM p.Gln448Arg (c.1343A>G)?

AlphaMissense predicts likely benign (score 0.0755) — an in-silico prediction, not a clinical call.

CHM p.Gln448Arg

c.1343A>G · rs1215519356 · VCV1968675

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0755 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0755	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -7.66	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 1.5	GERP -0.59, phastCons 0.94
Regional constraint	o/e 0.95	unconstrained · MANE · 183 kb · p 0.28 · regional, not allelic
Overall
CADD	6.706	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CHM
Protein: p.Gln448Arg
Coding: c.1343A>G
MANE Select: NM_000390
dbSNP: rs1215519356
Type: single nucleotide variant
Location: chrX:85901090 (GRCh38)
Structure: AlphaFold pLDDT 81.05

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

Similar variants

CHM p.Gln448Ter Pathogenic ★★ same residue
CHM p.Gln448fs Likely 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
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-gln448arg (accessed [today's date]).

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