Is CHPT1 p.Pro86Arg (c.257C>G) pathogenic?

CHPT1 p.Pro86Arg (c.257C>G) is classified Uncertain significance in CHPT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). AlphaMissense: ambiguous (0.3472); Very rare (popmax 0.00941%, nfe).

How common is CHPT1 p.Pro86Arg (c.257C>G) in the general population?

CHPT1 p.Pro86Arg (c.257C>G) is very rare (popmax 0.00941%, nfe) (gnomAD).

What do computational predictors say about CHPT1 p.Pro86Arg (c.257C>G)?

AlphaMissense predicts ambiguous (score 0.3472) — an in-silico prediction, not a clinical call.

CHPT1 p.Pro86Arg

c.257C>G · rs755098314 · VCV2515434

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3472 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00941%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3472	ambiguous
REVEL	0.256	benign-leaning
SaProt	LLR -11.30	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.9	GERP 0.96, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 31 kb · p 0.072 · regional, not allelic
Overall
CADD	27.5	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 0.00941% European (non-Finnish) · 108/1,148,016 alleles

Filtering AF 0.00796% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00739%

Overall 0.00743% 114/1,535,188 alleles · very rare exomes 107/1,383,070 · genomes 7/152,118 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00941%	10,630
Remaining individualsnot grpmax-eligible	0.00842%	11,870
African / African-American	0.00142%	70,336

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.Pro86Arg
Coding: c.257C>G
MANE Select: NM_020244
dbSNP: rs755098314
Type: single nucleotide variant
Location: chr12:101698118 (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-pro86arg (accessed [today's date]).

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