Is CPD p.Phe317Leu (c.951C>G) pathogenic?

CPD p.Phe317Leu (c.951C>G) is classified Uncertain significance in CPD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-01). AlphaMissense: likely pathogenic (0.9979); Ultra-rare (popmax 0.0317%, amr).

How common is CPD p.Phe317Leu (c.951C>G) in the general population?

CPD p.Phe317Leu (c.951C>G) is ultra-rare (popmax 0.0317%, amr) (gnomAD).

What do computational predictors say about CPD p.Phe317Leu (c.951C>G)?

AlphaMissense predicts likely pathogenic (score 0.9979) — an in-silico prediction, not a clinical call.

CPD p.Phe317Leu

c.951C>G · rs200206773 · VCV2393486

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9979 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0317%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9979	likely pathogenic · top 3% in CPD
REVEL	0.243	benign-leaning
SaProt	LLR -12.47	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 2.7	GERP 0.88, phastCons 1
Overall
CADD	24.3	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 0.0317% Admixed American · 19/59,982 alleles

Filtering AF 0.0207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0172%

Overall 0.0149% 241/1,613,750 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0317%	3,157
European (non-Finnish)	0.0183%	5,463
Remaining individualsnot grpmax-eligible	0.0048%	20,829
African / African-American	0.00401%	24,944

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: CPD
Protein: p.Phe317Leu
Coding: c.951C>G
MANE Select: NM_004839 · reported on NM_001304
dbSNP: rs200206773
Type: single nucleotide variant
Location: chr17:30385193 (GRCh38)
Structure: AlphaFold pLDDT 89.20

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

Similar variants

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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
HOMER2 p.Glu255Asp Uncertain significance ★★ ⚠ same type
HOMER2 p.Glu274Lys 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-phe317leu (accessed [today's date]).

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