Is CHM p.Ser233Pro (c.697T>C) pathogenic?

CHM p.Ser233Pro (c.697T>C) is classified Uncertain significance in CHM (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-07). AlphaMissense: likely benign (0.2594); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CHM p.Ser233Pro (c.697T>C)?

CHM p.Ser233Pro (c.697T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CHM p.Ser233Pro (c.697T>C) in the general population?

CHM p.Ser233Pro (c.697T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHM p.Ser233Pro (c.697T>C)?

AlphaMissense predicts likely benign (score 0.2594) — an in-silico prediction, not a clinical call.

CHM p.Ser233Pro

c.697T>C · rs2520271817 · VCV2495012

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2594 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2594	likely benign
REVEL	0.436	indeterminate
SaProt	LLR -7.27	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 183 kb · p 0.28 · regional, not allelic
Overall
CADD	21.4	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.Ser233Pro
Coding: c.697T>C
MANE Select: NM_000390
dbSNP: rs2520271817
Type: single nucleotide variant
Location: chrX:85963670 (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.Ser233Ter Pathogenic ★ 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-ser233pro (accessed [today's date]).

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