Is CPD p.Arg57Pro (c.170G>C) pathogenic?

CPD p.Arg57Pro (c.170G>C) is classified Uncertain significance in CPD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-07). AlphaMissense: likely pathogenic (0.6204); Absent from gnomAD v4.1.

How common is CPD p.Arg57Pro (c.170G>C) in the general population?

CPD p.Arg57Pro (c.170G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CPD p.Arg57Pro (c.170G>C)?

AlphaMissense predicts likely pathogenic (score 0.6204) — an in-silico prediction, not a clinical call.

CPD p.Arg57Pro

c.170G>C · rs2509685898 · VCV2299968

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6204 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6204	likely pathogenic
REVEL	0.034	moderately benign-leaning
SaProt	LLR -13.89	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -1.6, phastCons 1
Overall
CADD	21.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CPD
Protein: p.Arg57Pro
Coding: c.170G>C
MANE Select: NM_004839 · reported on NM_001304
dbSNP: rs2509685898
Type: single nucleotide variant
Location: chr17:30379150 (GRCh38)
Structure: AlphaFold pLDDT 89.20
Residue 57: the wh1 domain

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

Similar variants

HOMER2 p.Ile57Leu Uncertain significance ★ ⚠ same residue
HOMER2 p.Ile57Thr Uncertain significance ★ ⚠ same residue
HOMER2 p.Arg208Cys Uncertain significance ★★ ⚠ same type
HOMER2 p.Arg213Trp Uncertain significance ★★ ⚠ same type
HOMER2 p.Arg215His Uncertain significance ★★ ⚠ same type
HOMER2 p.Arg309Cys Uncertain significance ★★ ⚠ same type
HOMER2 p.Arg334Gln Uncertain significance ★★ ⚠ same type
HOMER2 p.Asn235Lys 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/cpd-p-arg57pro (accessed [today's date]).

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