Is CCDC92 p.His288Gln (c.864C>A) pathogenic?

CCDC92 p.His288Gln (c.864C>A) is classified Uncertain significance in CCDC92 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-04). AlphaMissense: ambiguous (0.4128); Very rare (popmax 0.00133%, afr).

How common is CCDC92 p.His288Gln (c.864C>A) in the general population?

CCDC92 p.His288Gln (c.864C>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about CCDC92 p.His288Gln (c.864C>A)?

AlphaMissense predicts ambiguous (score 0.4128) — an in-silico prediction, not a clinical call.

CCDC92 p.His288Gln

c.864C>A · rs750311604 · VCV2615786

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4128 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4128	ambiguous
REVEL	0.216	benign-leaning
SaProt	LLR -6.85	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.2	GERP -3.4, phastCons 0.89
Regional constraint	o/e 0.91	unconstrained · MANE · 7,244 bp · p 0.054 · regional, not allelic
Overall
CADD	18.12	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 0.00133% African / African-American · 1/75,018 alleles

Overall 0.000137% 2/1,457,484 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,018
European (non-Finnish)	8.48e-05%	1,179,601

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: CCDC92
Protein: p.His288Gln
Coding: c.864C>A
MANE Select: NM_025140
dbSNP: rs750311604
Type: single nucleotide variant
Location: chr12:123937190 (GRCh38)
Gene constraint: LOEUF 0.738 · pLI 0.25 (gnomAD)
Structure: AlphaFold pLDDT 73.80

Full CCDC92 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC92 p.Ala114Thr Uncertain significance ★ ⚠ same type
CCDC92 p.Ala178Asp Uncertain significance ★ ⚠ same type
CCDC92 p.Ala226Val Uncertain significance ★ ⚠ same type
CCDC92 p.Ala269Thr Uncertain significance ★ ⚠ same type
CCDC92 p.Ala93Val Uncertain significance ★ ⚠ same type
CCDC92 p.Arg203His Uncertain significance ★ ⚠ same type
CCDC92 p.Arg223Gly Uncertain significance ★ ⚠ same type
CCDC92 p.Arg234Gln 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/ccdc92-p-his288gln (accessed [today's date]).

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