Is CHPF2 p.Cys271Phe (c.812G>T) pathogenic?

CHPF2 p.Cys271Phe (c.812G>T) is classified Uncertain significance in CHPF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-13). AlphaMissense: likely pathogenic (0.9964); Absent from gnomAD v4.1.

How common is CHPF2 p.Cys271Phe (c.812G>T) in the general population?

CHPF2 p.Cys271Phe (c.812G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CHPF2 p.Cys271Phe (c.812G>T)?

AlphaMissense predicts likely pathogenic (score 0.9964) — an in-silico prediction, not a clinical call.

CHPF2 p.Cys271Phe

c.812G>T · VCV4653504

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9964 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9964	likely pathogenic · top 1% in CHPF2
REVEL	0.668	pathogenic-leaning
SaProt	LLR -15.36	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 4,666 bp · p 0.76 · regional, not allelic
Overall
CADD	28.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: CHPF2
Protein: p.Cys271Phe
Coding: c.812G>T
MANE Select: NM_019015
Type: single nucleotide variant
Location: chr7:151235596 (GRCh38)
Gene constraint: LOEUF 1.136 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.86

Full CHPF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHPF2 p.Arg254His Benign ★★ same type
CHPF2 p.Arg460Gln Benign/Likely benign ★★ same type
CHPF2 p.Ala189Ser Uncertain significance ★ ⚠ same type
CHPF2 p.Ala216Thr Uncertain significance ★ ⚠ same type
CHPF2 p.Ala220Thr Uncertain significance ★ ⚠ same type
CHPF2 p.Ala352Gly Uncertain significance ★ ⚠ same type
CHPF2 p.Ala406Val Uncertain significance ★ ⚠ same type
CHPF2 p.Ala547Pro 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/chpf2-p-cys271phe (accessed [today's date]).

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