Is CPD p.Arg1059His (c.3176G>A) pathogenic?

CPD p.Arg1059His (c.3176G>A) is classified Likely benign in CPD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). AlphaMissense: likely benign (0.0603); Very rare (popmax 0.00329%, sas).

How common is CPD p.Arg1059His (c.3176G>A) in the general population?

CPD p.Arg1059His (c.3176G>A) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about CPD p.Arg1059His (c.3176G>A)?

AlphaMissense predicts likely benign (score 0.0603) — an in-silico prediction, not a clinical call.

CPD p.Arg1059His

c.3176G>A · VCV3496327

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0603 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0603	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -7.50	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 -0.49	GERP -5.3
Overall
CADD	4.772	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 0.00329% South Asian · 3/91,068 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000806% 13/1,613,872 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,356
Finnishnot grpmax-eligible	0.00312%	32,011
African / African-American	0.00267%	37,457
Admixed American	0.00167%	59,984
Remaining individualsnot grpmax-eligible	0.0016%	62,478
European (non-Finnish)	0.000339%	294,988

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.Arg1059His
Coding: c.3176G>A
MANE Select: NM_004839 · reported on NM_001304
Type: single nucleotide variant
Location: chr17:30451817 (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-arg1059his (accessed [today's date]).

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