Is CCDC93 p.Val70Ile (c.208G>A) pathogenic?

CCDC93 p.Val70Ile (c.208G>A) is classified Uncertain significance in CCDC93 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-23). AlphaMissense: likely benign (0.1162); Very rare (popmax 8.48e-05%, nfe).

How common is CCDC93 p.Val70Ile (c.208G>A) in the general population?

CCDC93 p.Val70Ile (c.208G>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CCDC93 p.Val70Ile (c.208G>A)?

AlphaMissense predicts likely benign (score 0.1162) — an in-silico prediction, not a clinical call.

CCDC93 p.Val70Ile

c.208G>A · VCV3828953

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1162 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1162	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -10.02	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 0.56, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 94 kb · p 0.0042 · regional, not allelic
Overall
CADD	21.2	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 8.48e-05% European (non-Finnish) · 1/1,178,824 alleles

Overall 6.85e-05% 1/1,460,490 alleles · very rare

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.Val70Ile
Coding: c.208G>A
MANE Select: NM_019044
Type: single nucleotide variant
Location: chr2:118006765 (GRCh38)
Gene constraint: LOEUF 0.986 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.49 · 4 PDB
Residue 70: the 'sufficient for interaction with ccdc22' 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.Ala628Val Uncertain significance ★ ⚠ same type
CCDC93 p.Arg126Gly 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-val70ile (accessed [today's date]).

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