Is CPD p.His671Gln (c.2013T>A) pathogenic?

CPD p.His671Gln (c.2013T>A) is classified Uncertain significance in CPD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-01). AlphaMissense: likely pathogenic (0.9957); Very rare (popmax 0.00017%, nfe).

How common is CPD p.His671Gln (c.2013T>A) in the general population?

CPD p.His671Gln (c.2013T>A) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about CPD p.His671Gln (c.2013T>A)?

AlphaMissense predicts likely pathogenic (score 0.9957) — an in-silico prediction, not a clinical call.

CPD p.His671Gln

c.2013T>A · rs759855143 · VCV2554826

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9957 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9957	likely pathogenic · top 4% in CPD
REVEL	0.376	indeterminate
SaProt	LLR -9.23	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 -0.15	GERP -3.4, phastCons 0.73
Overall
CADD	21.8	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 0.00017% European (non-Finnish) · 2/1,179,718 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,440 alleles · very rare

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.His671Gln
Coding: c.2013T>A
MANE Select: NM_004839 · reported on NM_001304
dbSNP: rs759855143
Type: single nucleotide variant
Location: chr17:30427554 (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-his671gln (accessed [today's date]).

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