Is CPD p.Arg1336Trp (c.4006C>T) pathogenic?

CPD p.Arg1336Trp (c.4006C>T) is classified Uncertain significance in CPD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-14). AlphaMissense: likely pathogenic (0.6348); Very rare (popmax 0.00769%, sas).

How common is CPD p.Arg1336Trp (c.4006C>T) in the general population?

CPD p.Arg1336Trp (c.4006C>T) is very rare (popmax 0.00769%, sas) (gnomAD).

What do computational predictors say about CPD p.Arg1336Trp (c.4006C>T)?

AlphaMissense predicts likely pathogenic (score 0.6348) — an in-silico prediction, not a clinical call.

CPD p.Arg1336Trp

c.4006C>T · VCV4006150

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6348 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00769%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6348	likely pathogenic
REVEL	0.241	benign-leaning
SaProt	LLR -11.08	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 6	GERP 2.1, phastCons 1
Overall
CADD	27.5	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 0.00769% South Asian · 7/91,084 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00118% 19/1,613,830 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00769%	13,012
African / African-American	0.00134%	74,874
European (non-Finnish)	0.000932%	107,264

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.Arg1336Trp
Coding: c.4006C>T
MANE Select: NM_004839 · reported on NM_001304
Type: single nucleotide variant
Location: chr17:30464677 (GRCh38)
Structure: AlphaFold pLDDT 89.20

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

Similar variants

CPD p.Arg1336Gln 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
HOMER2 p.Glu255Asp 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-arg1336trp (accessed [today's date]).

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