Is CHPF p.Gln697Arg (c.2090A>G) pathogenic?

CHPF p.Gln697Arg (c.2090A>G) is classified Uncertain significance in CHPF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-11). AlphaMissense: likely benign (0.075); Ultra-rare (popmax 0.0164%, mid).

How common is CHPF p.Gln697Arg (c.2090A>G) in the general population?

CHPF p.Gln697Arg (c.2090A>G) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about CHPF p.Gln697Arg (c.2090A>G)?

AlphaMissense predicts likely benign (score 0.075) — an in-silico prediction, not a clinical call.

CHPF p.Gln697Arg

c.2090A>G · VCV4228283

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.075 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.075	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -2.09	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 3.4	GERP 1.7, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 4,044 bp · p 0.00017 · regional, not allelic
Overall
CADD	21.3	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000868% 14/1,613,788 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
African / African-American	0.004%	24,981
South Asian	0.0022%	45,548
European (non-Finnish)	0.000678%	147,498

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.Gln697Arg
Coding: c.2090A>G
MANE Select: NM_024536
Type: single nucleotide variant
Location: chr2:219539621 (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-gln697arg (accessed [today's date]).

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