Is CHPF p.Glu698Lys (c.2092G>A) pathogenic?

CHPF p.Glu698Lys (c.2092G>A) is classified Uncertain significance in CHPF (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-16). AlphaMissense: likely benign (0.2175); Ultra-rare (popmax 0.0533%, amr).

How common is CHPF p.Glu698Lys (c.2092G>A) in the general population?

CHPF p.Glu698Lys (c.2092G>A) is ultra-rare (popmax 0.0533%, amr) (gnomAD).

What do computational predictors say about CHPF p.Glu698Lys (c.2092G>A)?

AlphaMissense predicts likely benign (score 0.2175) — an in-silico prediction, not a clinical call.

CHPF p.Glu698Lys

c.2092G>A · rs143750392 · VCV2239257

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2175 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0533%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2175	likely benign
REVEL	0.088	moderately benign-leaning
SaProt	LLR -6.91	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 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	22.8	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 0.0533% Admixed American · 32/60,034 alleles

Filtering AF 0.0387% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0338%

Overall 0.0219% 353/1,613,938 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0533%	1,876
Remaining individualsnot grpmax-eligible	0.0256%	3,906
South Asian	0.0242%	4,141
European (non-Finnish)	0.0228%	4,387
African / African-American	0.012%	8,342
East Asian	0.0111%	8,974

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.Glu698Lys
Coding: c.2092G>A
MANE Select: NM_024536
dbSNP: rs143750392
Type: single nucleotide variant
Location: chr2:219539619 (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.Glu698Gln 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-glu698lys (accessed [today's date]).

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