Is CHPF2 p.Arg90Trp (c.268C>T) pathogenic?

CHPF2 p.Arg90Trp (c.268C>T) is classified Uncertain significance in CHPF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-07). AlphaMissense: likely pathogenic (0.7789); Ultra-rare (popmax 0.0539%, amr).

How common is CHPF2 p.Arg90Trp (c.268C>T) in the general population?

CHPF2 p.Arg90Trp (c.268C>T) is ultra-rare (popmax 0.0539%, amr) (gnomAD).

What do computational predictors say about CHPF2 p.Arg90Trp (c.268C>T)?

AlphaMissense predicts likely pathogenic (score 0.7789) — an in-silico prediction, not a clinical call.

CHPF2 p.Arg90Trp

c.268C>T · VCV3492436

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7789 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0539%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7789	likely pathogenic
REVEL	0.495	indeterminate
SaProt	LLR -9.98	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
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 1.01	unconstrained · MANE · 4,666 bp · p 0.76 · regional, not allelic
Overall
CADD	29.9	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 0.0539% Admixed American · 28/51,922 alleles

Filtering AF 0.0382% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.033%

Overall 0.00402% 62/1,543,698 alleles · ultra-rare exomes 49/1,391,502 · genomes 13/152,196 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0539%	1,854
African / African-American	0.00685%	14,602
Remaining individualsnot grpmax-eligible	0.00505%	19,789
East Asian	0.00453%	22,076
European (non-Finnish)	0.0021%	47,577

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: CHPF2
Protein: p.Arg90Trp
Coding: c.268C>T
MANE Select: NM_019015
Type: single nucleotide variant
Location: chr7:151235052 (GRCh38)
Gene constraint: LOEUF 1.136 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.86

Full CHPF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CHPF2 p.Arg254His Benign ★★ same type
CHPF2 p.Arg460Gln Benign/Likely benign ★★ same type
CHPF2 p.Ala189Ser Uncertain significance ★ ⚠ same type
CHPF2 p.Ala216Thr Uncertain significance ★ ⚠ same type
CHPF2 p.Ala220Thr Uncertain significance ★ ⚠ same type
CHPF2 p.Ala352Gly Uncertain significance ★ ⚠ same type
CHPF2 p.Ala406Val Uncertain significance ★ ⚠ same type
CHPF2 p.Ala547Pro 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/chpf2-p-arg90trp (accessed [today's date]).

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