Is CHPF p.Arg730His (c.2189G>A) pathogenic?

CHPF p.Arg730His (c.2189G>A) is classified Uncertain significance in CHPF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-15). AlphaMissense: likely benign (0.083); Ultra-rare (popmax 0.0981%, eas).

How common is CHPF p.Arg730His (c.2189G>A) in the general population?

CHPF p.Arg730His (c.2189G>A) is ultra-rare (popmax 0.0981%, eas) (gnomAD).

What do computational predictors say about CHPF p.Arg730His (c.2189G>A)?

AlphaMissense predicts likely benign (score 0.083) — an in-silico prediction, not a clinical call.

CHPF p.Arg730His

c.2189G>A · rs76494878 · VCV2394960

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.083 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0981%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.083	likely benign
REVEL	0.069	moderately benign-leaning
SaProt	LLR -9.66	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.18	GERP -3.5, phastCons 0.36
Regional constraint	o/e 0.88	unconstrained · MANE · 4,044 bp · p 0.00017 · regional, not allelic
Overall
CADD	17.33	PHRED · no single calibrated threshold — expert panels disagree

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

Grpmax group 0.0981% East Asian · 44/44,874 alleles

Filtering AF 0.075% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0669%

Overall 0.0273% 441/1,613,764 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0981%	1,020
African / African-American	0.0693%	1,444
European (non-Finnish)	0.0262%	3,818
Remaining individualsnot grpmax-eligible	0.0256%	3,906
Admixed American	0.0167%	6,001
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,396
Finnishnot grpmax-eligible	0.0047%	21,261
South Asian	0.00329%	30,357

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.Arg730His
Coding: c.2189G>A
MANE Select: NM_024536
dbSNP: rs76494878
Type: single nucleotide variant
Location: chr2:219539522 (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-arg730his (accessed [today's date]).

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