Is CHPT1 p.Leu26Val (c.76C>G) pathogenic?

CHPT1 p.Leu26Val (c.76C>G) is classified Uncertain significance in CHPT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-09). AlphaMissense: ambiguous (0.3972); Absent from gnomAD v4.1.

How common is CHPT1 p.Leu26Val (c.76C>G) in the general population?

CHPT1 p.Leu26Val (c.76C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHPT1 p.Leu26Val (c.76C>G)?

AlphaMissense predicts ambiguous (score 0.3972) — an in-silico prediction, not a clinical call.

CHPT1 p.Leu26Val

c.76C>G · rs1212124769 · VCV3144537

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3972 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.3972	ambiguous
REVEL	0.338	indeterminate
SaProt	LLR -9.86	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP -1.2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 31 kb · p 0.072 · regional, not allelic
Overall
CADD	25.3	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: CHPT1
Protein: p.Leu26Val
Coding: c.76C>G
MANE Select: NM_020244
dbSNP: rs1212124769
Type: single nucleotide variant
Location: chr12:101697937 (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-leu26val (accessed [today's date]).

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