Is CHPF p.Glu700Lys (c.2098G>A) pathogenic?

CHPF p.Glu700Lys (c.2098G>A) is classified Uncertain significance in CHPF (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-06). AlphaMissense: likely benign (0.2505); Ultra-rare (popmax 0.0552%, nfe).

How common is CHPF p.Glu700Lys (c.2098G>A) in the general population?

CHPF p.Glu700Lys (c.2098G>A) is ultra-rare (popmax 0.0552%, nfe) (gnomAD).

What do computational predictors say about CHPF p.Glu700Lys (c.2098G>A)?

AlphaMissense predicts likely benign (score 0.2505) — an in-silico prediction, not a clinical call.

CHPF p.Glu700Lys

c.2098G>A · rs755993200 · VCV2377151

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2505 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0552%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2505	likely benign
REVEL	0.204	benign-leaning
SaProt	LLR -9.02	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 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 4,044 bp · p 0.00017 · regional, not allelic
Overall
CADD	27.0	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 0.0552% European (non-Finnish) · 651/1,179,968 alleles

Filtering AF 0.0516% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0502%

Overall 0.0425% 686/1,613,760 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0552%	1,813
Remaining individualsnot grpmax-eligible	0.0304%	3,288
African / African-American	0.016%	6,245
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,598
Finnishnot grpmax-eligible	0.00313%	31,912
Admixed American	0.00167%	60,014

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.Glu700Lys
Coding: c.2098G>A
MANE Select: NM_024536
dbSNP: rs755993200
Type: single nucleotide variant
Location: chr2:219539613 (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.Glu700Val 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-glu700lys (accessed [today's date]).

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