Is CCDC92 p.Ala269Thr (c.805G>A) pathogenic?

CCDC92 p.Ala269Thr (c.805G>A) is classified Uncertain significance in CCDC92 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-11). AlphaMissense: likely benign (0.1045); Rare (popmax 0.197%, mid).

How common is CCDC92 p.Ala269Thr (c.805G>A) in the general population?

CCDC92 p.Ala269Thr (c.805G>A) is rare (popmax 0.197%, mid) (gnomAD).

What do computational predictors say about CCDC92 p.Ala269Thr (c.805G>A)?

AlphaMissense predicts likely benign (score 0.1045) — an in-silico prediction, not a clinical call.

CCDC92 p.Ala269Thr

c.805G>A · rs367836688 · VCV2347127

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1045 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.197%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1045	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -5.81	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 3.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 7,244 bp · p 0.054 · regional, not allelic
Overall
CADD	19.43	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 0.197% Middle Eastern · 12/6,082 alleles

Filtering AF 0.114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0892%

Overall 0.0276% 444/1,610,874 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.197%	507
Ashkenazi Jewishnot grpmax-eligible	0.0372%	2,689
Finnishnot grpmax-eligible	0.0343%	2,918
South Asian	0.034%	2,937
Remaining individualsnot grpmax-eligible	0.032%	3,123
European (non-Finnish)	0.0283%	3,532
African / African-American	0.0147%	6,810
Admixed American	0.00667%	14,998

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.Ala269Thr
Coding: c.805G>A
MANE Select: NM_025140
dbSNP: rs367836688
Type: single nucleotide variant
Location: chr12:123937249 (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.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
CCDC92 p.Arg250Thr 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-ala269thr (accessed [today's date]).

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