Is CCDC152 p.Arg231His (c.692G>A) pathogenic?

CCDC152 p.Arg231His (c.692G>A) is classified Uncertain significance in CCDC152 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-24). AlphaMissense: likely benign (0.0882); Ultra-rare (popmax 0.085%, afr).

How common is CCDC152 p.Arg231His (c.692G>A) in the general population?

CCDC152 p.Arg231His (c.692G>A) is ultra-rare (popmax 0.085%, afr) (gnomAD).

What do computational predictors say about CCDC152 p.Arg231His (c.692G>A)?

AlphaMissense predicts likely benign (score 0.0882) — an in-silico prediction, not a clinical call.

CCDC152 p.Arg231His

c.692G>A · rs201244796 · VCV2218220

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0882 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.085%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0882	likely benign
REVEL	0.104	moderately benign-leaning
SaProt	LLR -6.66	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 1.8	phastCons 0.94
Regional constraint	o/e 0.89	unconstrained · MANE · 41 kb · p 0.053 · regional, not allelic
Overall
CADD	21.9	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 0.085% African / African-American · 62/72,974 alleles

Filtering AF 0.068% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0619%

Overall 0.0138% 214/1,550,594 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.085%	1,177
East Asian	0.0734%	1,363
Middle Eastern	0.0666%	1,502
Remaining individualsnot grpmax-eligible	0.0266%	3,753
Admixed American	0.0177%	5,660
European (non-Finnish)	0.00785%	12,738
South Asian	0.00238%	41,976
Finnishnot grpmax-eligible	0.00167%	59,858

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: CCDC152
Protein: p.Arg231His
Coding: c.692G>A
MANE Select: NM_001134848
dbSNP: rs201244796
Type: single nucleotide variant
Location: chr5:42799708 (GRCh38)
Gene constraint: LOEUF 1.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.17

Full CCDC152 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SELENOP p.Gly230= Benign ★★ same type
CCDC152 p.Ala116Asp Uncertain significance ★ ⚠ same type
CCDC152 p.Ala192Pro Uncertain significance ★ ⚠ same type
CCDC152 p.Ala228Glu Uncertain significance ★ ⚠ same type
CCDC152 p.Arg253Trp Uncertain significance ★ ⚠ same type
CCDC152 p.Cys66Ser Uncertain significance ★ ⚠ same type
CCDC152 p.Cys8Tyr Uncertain significance ★ ⚠ same type
CCDC152 p.Gln26Lys 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/ccdc152-p-arg231his (accessed [today's date]).

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