Is CHM p.Arg488Leu (c.1463G>T) pathogenic?

CHM p.Arg488Leu (c.1463G>T) is classified Uncertain significance in CHM (ClinVar, Single submitter, 1 submitter; last evaluated 2018-09-10). AlphaMissense: likely benign (0.2803); Absent from gnomAD v4.1.

How common is CHM p.Arg488Leu (c.1463G>T) in the general population?

CHM p.Arg488Leu (c.1463G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHM p.Arg488Leu (c.1463G>T)?

AlphaMissense predicts likely benign (score 0.2803) — an in-silico prediction, not a clinical call.

CHM p.Arg488Leu

c.1463G>T · rs1392097406 · VCV866185

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2803 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2803	likely benign
REVEL	0.497	indeterminate
SaProt	LLR -11.55	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.36 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.5	GERP -0.78, phastCons 0.99
Regional constraint	o/e 0.95	unconstrained · MANE · 183 kb · p 0.28 · regional, not allelic
Overall
CADD	21.7	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

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.Arg488Leu
Coding: c.1463G>T
MANE Select: NM_000390
dbSNP: rs1392097406
Type: single nucleotide variant
Location: chrX:85894235 (GRCh38)
Structure: AlphaFold pLDDT 81.05

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

Similar variants

CHM p.Arg488= Likely benign ★ 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
CHM c.1244+2T>A 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-arg488leu (accessed [today's date]).

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