Is CHPF p.Arg627His (c.1880G>A) pathogenic?

CHPF p.Arg627His (c.1880G>A) is classified Uncertain significance in CHPF (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-11). AlphaMissense: ambiguous (0.5458); Ultra-rare (popmax 0.0493%, mid).

How common is CHPF p.Arg627His (c.1880G>A) in the general population?

CHPF p.Arg627His (c.1880G>A) is ultra-rare (popmax 0.0493%, mid) (gnomAD).

What do computational predictors say about CHPF p.Arg627His (c.1880G>A)?

AlphaMissense predicts ambiguous (score 0.5458) — an in-silico prediction, not a clinical call.

CHPF p.Arg627His

c.1880G>A · rs772864126 · VCV2592191

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5458 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, mid)

Computational evidence

Protein change
AlphaMissense	0.5458	ambiguous
REVEL	0.595	indeterminate
SaProt	LLR -12.42	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 4,044 bp · p 0.00017 · regional, not allelic
Overall
CADD	32.0	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 0.0493% Middle Eastern · 3/6,084 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00905%

Overall 0.00917% 148/1,613,430 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0493%	2,028
East Asian	0.0134%	7,481
European (non-Finnish)	0.0113%	8,872
Remaining individualsnot grpmax-eligible	0.0032%	31,240
African / African-American	0.00267%	37,471
Admixed American	0.00167%	60,010
South Asian	0.0011%	91,088

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.Arg627His
Coding: c.1880G>A
MANE Select: NM_024536
dbSNP: rs772864126
Type: single nucleotide variant
Location: chr2:219539831 (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.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
CHPF p.Ala530Gly 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-arg627his (accessed [today's date]).

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