Is CCDC88B p.Pro693Thr (c.2077C>A) pathogenic?

CCDC88B p.Pro693Thr (c.2077C>A) is classified Uncertain significance in CCDC88B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-26). AlphaMissense: likely benign (0.0716); Ultra-rare (popmax 0.0613%, afr).

How common is CCDC88B p.Pro693Thr (c.2077C>A) in the general population?

CCDC88B p.Pro693Thr (c.2077C>A) is ultra-rare (popmax 0.0613%, afr) (gnomAD).

What do computational predictors say about CCDC88B p.Pro693Thr (c.2077C>A)?

AlphaMissense predicts likely benign (score 0.0716) — an in-silico prediction, not a clinical call.

CCDC88B p.Pro693Thr

c.2077C>A · VCV4649786

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0716 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0613%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0716	likely benign
REVEL	0.014	strongly benign-leaning
SaProt	LLR -7.28	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 -1.5	GERP -1.5
Regional constraint	o/e 0.93	unconstrained · MANE · 17 kb · p 0.0012 · regional, not allelic
Overall
CADD	0.309	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 0.0613% African / African-American · 46/75,018 alleles

Filtering AF 0.0472% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0422%

Overall 0.00304% 49/1,612,928 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0613%	1,631
Admixed American	0.00502%	19,931

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: CCDC88B
Protein: p.Pro693Thr
Coding: c.2077C>A
MANE Select: NM_032251
Type: single nucleotide variant
Location: chr11:64344618 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.19
Residue 693: the 'disordered' region

Full CCDC88B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC88B p.Arg328Ser Uncertain significance ★★ ⚠ same type
CCDC88B p.Leu1234= Benign ★★ same type
CCDC88B p.Ala1025Thr Uncertain significance ★ ⚠ same type
CCDC88B p.Ala1025Val Uncertain significance ★ ⚠ same type
CCDC88B p.Ala1059Val Uncertain significance ★ ⚠ same type
CCDC88B p.Ala1112Thr Uncertain significance ★ ⚠ same type
CCDC88B p.Ala1132Val Uncertain significance ★ ⚠ same type
CCDC88B p.Ala1251Ser 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/ccdc88b-p-pro693thr (accessed [today's date]).

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