Is CCDC88A p.Pro27Ser (c.79C>T) pathogenic?

CCDC88A p.Pro27Ser (c.79C>T) is classified Uncertain significance in CCDC88A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-17). AlphaMissense: likely benign (0.0836); Very rare (popmax 0.00267%, afr).

How common is CCDC88A p.Pro27Ser (c.79C>T) in the general population?

CCDC88A p.Pro27Ser (c.79C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about CCDC88A p.Pro27Ser (c.79C>T)?

AlphaMissense predicts likely benign (score 0.0836) — an in-silico prediction, not a clinical call.

CCDC88A p.Pro27Ser

c.79C>T · rs763787555 · VCV3139532

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0836 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0836	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -5.97	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 8.5	GERP 0.89, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 209 bp · p 0.23 · regional, not allelic
Overall
CADD	23.0	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 0.00267% African / African-American · 2/74,888 alleles

Filtering AF 0.00172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.00198% 32/1,613,842 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,444
European (non-Finnish)	0.00246%	40,686
Remaining individualsnot grpmax-eligible	0.0016%	62,482

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: CCDC88A
Protein: p.Pro27Ser
Coding: c.79C>T
MANE Select: NM_001365480
dbSNP: rs763787555
Type: single nucleotide variant
Location: chr2:55418901 (GRCh38)
Gene constraint: LOEUF 0.25 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 67.09 · 1 PDB
Residue 27: the calponin-homology (ch) domain

Full CCDC88A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC88A p.Pro27His Uncertain significance ★ ⚠ same residue
CCDC88A p.Ala1536Thr Uncertain significance ★★ ⚠ same type
CCDC88A p.Ala155Val Uncertain significance ★★ ⚠ same type
CCDC88A p.Ala158Thr Uncertain significance ★★ ⚠ same type
CCDC88A p.Ala1770Val Uncertain significance ★★ ⚠ same type
CCDC88A p.Ala194Thr Uncertain significance ★★ ⚠ same type
CCDC88A p.Ala72Thr Uncertain significance ★★ ⚠ same type
CCDC88A p.Ala845Gly 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/ccdc88a-p-pro27ser (accessed [today's date]).

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