Is CHPF p.Arg596Cys (c.1786C>T) pathogenic?

CHPF p.Arg596Cys (c.1786C>T) is classified Uncertain significance in CHPF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-14). AlphaMissense: ambiguous (0.3963); Very rare (popmax 0.00267%, afr).

How common is CHPF p.Arg596Cys (c.1786C>T) in the general population?

CHPF p.Arg596Cys (c.1786C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about CHPF p.Arg596Cys (c.1786C>T)?

AlphaMissense predicts ambiguous (score 0.3963) — an in-silico prediction, not a clinical call.

CHPF p.Arg596Cys

c.1786C>T · VCV4002501

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3963 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3963	ambiguous
REVEL	0.233	benign-leaning
SaProt	LLR -12.83	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
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 0.88	unconstrained · MANE · 4,044 bp · p 0.00017 · regional, not allelic
Overall
CADD	33.0	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 0.00267% African / African-American · 2/74,956 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00155% 25/1,613,670 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,478
European (non-Finnish)	0.00186%	53,635
Finnishnot grpmax-eligible	0.00157%	63,676

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: CHPF
Protein: p.Arg596Cys
Coding: c.1786C>T
MANE Select: NM_024536
Type: single nucleotide variant
Location: chr2:219539925 (GRCh38)
Gene constraint: LOEUF 0.954 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.57 · 2 PDB

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

Similar variants

CHPF p.Arg596His Uncertain significance ★ ⚠ same residue
CHPF p.Glu699= Benign ★★ same type
CHPF p.Ser48Pro Benign/Likely benign ★★ same type
CHPF p.Ala206Ser Uncertain significance ★ ⚠ same type
CHPF p.Ala286Val Uncertain significance ★ ⚠ same type
CHPF p.Ala341Thr Uncertain significance ★ ⚠ same type
CHPF p.Ala343Gly Uncertain significance ★ ⚠ same type
CHPF p.Ala516Val 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/chpf-p-arg596cys (accessed [today's date]).

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