Is CCDC88C p.Glu826Val (c.2477A>T) pathogenic?

CCDC88C p.Glu826Val (c.2477A>T) is classified Uncertain significance in CCDC88C (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-01). AlphaMissense: ambiguous (0.3517); Very rare (popmax 8.48e-05%, nfe).

How common is CCDC88C p.Glu826Val (c.2477A>T) in the general population?

CCDC88C p.Glu826Val (c.2477A>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CCDC88C p.Glu826Val (c.2477A>T)?

AlphaMissense predicts ambiguous (score 0.3517) — an in-silico prediction, not a clinical call.

CCDC88C p.Glu826Val

c.2477A>T · rs760010675 · VCV1911744

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3517 · ACMG-weighted

gnomAD v4.1

Rare

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

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3517	ambiguous
REVEL	0.186	benign-leaning
SaProt	LLR -8.51	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 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 112 kb · p 5.2e-05 · regional, not allelic
Overall
CADD	25.3	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) · 1/1,179,894 alleles

Overall 6.2e-05% 1/1,613,032 alleles · very rare exomes 1/1,460,702 · genomes 0/152,330 · joint denominator

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: CCDC88C
Protein: p.Glu826Val
Coding: c.2477A>T
MANE Select: NM_001080414
dbSNP: rs760010675
Type: single nucleotide variant
Location: chr14:91313339 (GRCh38)
Gene constraint: LOEUF 0.759 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.69

Full CCDC88C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC88C c.3358-2A>C Likely pathogenic ★★ same type
CCDC88C c.4442-2A>G Likely pathogenic ★★ same type
CCDC88C c.4768+1G>T Likely pathogenic ★★ same type
CCDC88C p.Arg1701Ter Pathogenic/Likely pathogenic ★★ same type
CCDC88C p.Arg312Ter Pathogenic ★★ same type
CCDC88C p.Arg407Ter Pathogenic/Likely pathogenic ★★ same type
CCDC88C c.3358-5G>A Uncertain significance ★★ same type
CCDC88C p.Ala1102Thr 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/ccdc88c-p-glu826val (accessed [today's date]).

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