Is CPD p.Ile1325Val (c.3973A>G) pathogenic?

CPD p.Ile1325Val (c.3973A>G) is classified Uncertain significance in CPD (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-29). AlphaMissense: likely benign (0.1074); Very rare (popmax 0.004%, afr).

How common is CPD p.Ile1325Val (c.3973A>G) in the general population?

CPD p.Ile1325Val (c.3973A>G) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about CPD p.Ile1325Val (c.3973A>G)?

AlphaMissense predicts likely benign (score 0.1074) — an in-silico prediction, not a clinical call.

CPD p.Ile1325Val

c.3973A>G · rs148102054 · VCV2262280

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1074 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1074	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -6.11	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 9.4	GERP 0.91, phastCons 1
Overall
CADD	18.9	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 0.004% African / African-American · 3/75,004 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.00062% 10/1,613,932 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	25,001
Remaining individualsnot grpmax-eligible	0.0016%	62,492
European (non-Finnish)	0.000509%	196,647

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.Ile1325Val
Coding: c.3973A>G
MANE Select: NM_004839 · reported on NM_001304
dbSNP: rs148102054
Type: single nucleotide variant
Location: chr17:30464644 (GRCh38)
Structure: AlphaFold pLDDT 89.20

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

Similar variants

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
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-ile1325val (accessed [today's date]).

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