Is CHPT1 p.Ser9Ala (c.25T>G) pathogenic?

CHPT1 p.Ser9Ala (c.25T>G) is classified Uncertain significance in CHPT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-17). AlphaMissense: likely benign (0.0489); Very rare (popmax 0.00685%, sas).

How common is CHPT1 p.Ser9Ala (c.25T>G) in the general population?

CHPT1 p.Ser9Ala (c.25T>G) is very rare (popmax 0.00685%, sas) (gnomAD).

What do computational predictors say about CHPT1 p.Ser9Ala (c.25T>G)?

AlphaMissense predicts likely benign (score 0.0489) — an in-silico prediction, not a clinical call.

CHPT1 p.Ser9Ala

c.25T>G · rs980596608 · VCV2209193

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0489 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00685%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0489	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -3.89	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 0.088	GERP -2.2, phastCons 0.46
Regional constraint	o/e 0.92	unconstrained · MANE · 31 kb · p 0.072 · regional, not allelic
Overall
CADD	7.585	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 0.00685% South Asian · 2/29,218 alleles

Filtering AF 0.00208% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.00179% 22/1,229,502 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00685%	14,609
African / African-American	0.00636%	15,725
Remaining individualsnot grpmax-eligible	0.00447%	22,396
Admixed American	0.00438%	22,852
East Asian	0.0033%	30,260
European (non-Finnish)	0.00122%	82,299

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: CHPT1
Protein: p.Ser9Ala
Coding: c.25T>G
MANE Select: NM_020244
dbSNP: rs980596608
Type: single nucleotide variant
Location: chr12:101697886 (GRCh38)
Gene constraint: LOEUF 1.393 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.30 · 1 PDB

Full CHPT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHPT1 p.Phe341Leu Benign ★★ ⚠ same type
SYCP3 c.*205G>A Benign ★★ same type
SYCP3 p.Gln222= Benign ★★ same type
CHPT1 p.Ala147Ser Uncertain significance ★ ⚠ same type
CHPT1 p.Ala16Glu Uncertain significance ★ ⚠ same type
CHPT1 p.Ala210Pro Uncertain significance ★ ⚠ same type
CHPT1 p.Ala210Val Uncertain significance ★ ⚠ same type
CHPT1 p.Ala3Val 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/chpt1-p-ser9ala (accessed [today's date]).

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