Is CHTOP p.Pro209Ser (c.625C>T) pathogenic?

CHTOP p.Pro209Ser (c.625C>T) is classified Uncertain significance in CHTOP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-07). AlphaMissense: ambiguous (0.3423); Absent from gnomAD v4.1.

How common is CHTOP p.Pro209Ser (c.625C>T) in the general population?

CHTOP p.Pro209Ser (c.625C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHTOP p.Pro209Ser (c.625C>T)?

AlphaMissense predicts ambiguous (score 0.3423) — an in-silico prediction, not a clinical call.

CHTOP p.Pro209Ser

c.625C>T · VCV3833356

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3423 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3423	ambiguous
REVEL	0.198	benign-leaning
SaProt	LLR -11.74	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 0.55, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 2,861 bp · p 0.37 · regional, not allelic
Overall
CADD	24.9	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: CHTOP
Protein: p.Pro209Ser
Coding: c.625C>T
MANE Select: NM_015607
Type: single nucleotide variant
Location: chr1:153645147 (GRCh38)
Gene constraint: LOEUF 0.768 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.64

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

Similar variants

CHTOP p.Ala99Ser Uncertain significance ★ ⚠ same type
CHTOP p.Arg110Lys Uncertain significance ★ ⚠ same type
CHTOP p.Arg124Thr Uncertain significance ★ ⚠ same type
CHTOP p.Arg157Gln Uncertain significance ★ ⚠ same type
CHTOP p.Arg159His Uncertain significance ★ ⚠ same type
CHTOP p.Arg169His Uncertain significance ★ ⚠ same type
CHTOP p.Arg187Trp Uncertain significance ★ ⚠ same type
CHTOP p.Arg195Leu Uncertain significance ★ ⚠ 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/chtop-p-pro209ser (accessed [today's date]).

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