Is CCDC93 p.Met263Val (c.787A>G) pathogenic?

CCDC93 p.Met263Val (c.787A>G) is classified Uncertain significance in CCDC93 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-27). AlphaMissense: likely benign (0.0842); Rare (popmax 0.115%, eas).

How common is CCDC93 p.Met263Val (c.787A>G) in the general population?

CCDC93 p.Met263Val (c.787A>G) is rare (popmax 0.115%, eas) (gnomAD).

What do computational predictors say about CCDC93 p.Met263Val (c.787A>G)?

AlphaMissense predicts likely benign (score 0.0842) — an in-silico prediction, not a clinical call.

CCDC93 p.Met263Val

c.787A>G · VCV3487183

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0842 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.115%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0842	likely benign
REVEL	0.126	moderately benign-leaning
SaProt	LLR -4.21	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 5	GERP 2.8, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 94 kb · p 0.0042 · regional, not allelic
Overall
CADD	20.9	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 0.115% East Asian · 49/42,660 alleles

Filtering AF 0.0892% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0801%

Overall 0.0136% 214/1,571,880 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.115%	871
Middle Eastern	0.0838%	1,194
South Asian	0.0187%	5,334
Remaining individualsnot grpmax-eligible	0.0181%	5,536
European (non-Finnish)	0.0111%	8,975
Admixed American	0.00369%	27,118
African / African-American	0.0027%	37,014

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.Met263Val
Coding: c.787A>G
MANE Select: NM_019044
Type: single nucleotide variant
Location: chr2:117974864 (GRCh38)
Gene constraint: LOEUF 0.986 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.49 · 4 PDB
Residue 263: 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-met263val (accessed [today's date]).

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