Is CCDC93 p.Ala628Val (c.1883C>T) pathogenic?

CCDC93 p.Ala628Val (c.1883C>T) is classified Uncertain significance in CCDC93 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-16). AlphaMissense: likely benign (0.0827); Very rare (popmax 0.00446%, eas).

How common is CCDC93 p.Ala628Val (c.1883C>T) in the general population?

CCDC93 p.Ala628Val (c.1883C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about CCDC93 p.Ala628Val (c.1883C>T)?

AlphaMissense predicts likely benign (score 0.0827) — an in-silico prediction, not a clinical call.

CCDC93 p.Ala628Val

c.1883C>T · rs1319780623 · VCV3139647

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0827 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0827	likely benign
REVEL	0.134	moderately benign-leaning
SaProt	LLR -9.77	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 8.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 94 kb · p 0.0042 · regional, not allelic
Overall
CADD	23.5	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 0.00446% East Asian · 2/44,866 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000548% 8/1,460,438 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,433
Admixed American	0.00334%	29,982
Remaining individualsnot grpmax-eligible	0.0016%	62,428
European (non-Finnish)	0.000254%	392,997

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: CCDC93
Protein: p.Ala628Val
Coding: c.1883C>T
MANE Select: NM_019044
dbSNP: rs1319780623
Type: single nucleotide variant
Location: chr2:117920356 (GRCh38)
Gene constraint: LOEUF 0.986 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.49 · 4 PDB
Residue 628: the 'sufficient for interaction with washc2c' region

Full CCDC93 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC93 p.Pro228Leu Benign ★★ same type
CCDC93 p.Ala226Val Uncertain significance ★ ⚠ same type
CCDC93 p.Ala262Thr Uncertain significance ★ ⚠ same type
CCDC93 p.Ala272Thr Uncertain significance ★ ⚠ same type
CCDC93 p.Ala370Thr Uncertain significance ★ ⚠ same type
CCDC93 p.Ala510Thr Uncertain significance ★ ⚠ same type
CCDC93 p.Arg126Gly Uncertain significance ★ ⚠ same type
CCDC93 p.Arg139His 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/ccdc93-p-ala628val (accessed [today's date]).

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