Is CHPT1 p.Val191Ile (c.571G>A) pathogenic?

CHPT1 p.Val191Ile (c.571G>A) is classified Uncertain significance in CHPT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-06). AlphaMissense: likely benign (0.2283); Very rare (popmax 0.000511%, nfe).

How common is CHPT1 p.Val191Ile (c.571G>A) in the general population?

CHPT1 p.Val191Ile (c.571G>A) is very rare (popmax 0.000511%, nfe) (gnomAD).

What do computational predictors say about CHPT1 p.Val191Ile (c.571G>A)?

AlphaMissense predicts likely benign (score 0.2283) — an in-silico prediction, not a clinical call.

CHPT1 p.Val191Ile

c.571G>A · rs1365941585 · VCV2333504

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2283 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000511%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2283	likely benign
REVEL	0.2	benign-leaning
SaProt	LLR -10.06	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 31 kb · p 0.072 · regional, not allelic
Overall
CADD	25.7	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

Grpmax group 0.000511% European (non-Finnish) · 6/1,174,136 alleles

Filtering AF 0.000184% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000121%

Overall 0.000414% 6/1,449,058 alleles · very rare

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.Val191Ile
Coding: c.571G>A
MANE Select: NM_020244
dbSNP: rs1365941585
Type: single nucleotide variant
Location: chr12:101716735 (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-val191ile (accessed [today's date]).

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