Is CCDC90B p.Ser28Pro (c.82T>C) pathogenic?

CCDC90B p.Ser28Pro (c.82T>C) is classified Uncertain significance in CCDC90B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-23). AlphaMissense: likely benign (0.0612); Ultra-rare (popmax 0.0495%, sas).

How common is CCDC90B p.Ser28Pro (c.82T>C) in the general population?

CCDC90B p.Ser28Pro (c.82T>C) is ultra-rare (popmax 0.0495%, sas) (gnomAD).

What do computational predictors say about CCDC90B p.Ser28Pro (c.82T>C)?

AlphaMissense predicts likely benign (score 0.0612) — an in-silico prediction, not a clinical call.

CCDC90B p.Ser28Pro

c.82T>C · VCV3264422

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0612 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0612	likely benign
REVEL	0.262	benign-leaning
SaProt	LLR -6.75	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 3.1	GERP 0.27, phastCons 0.94
Regional constraint	o/e 1.07	unconstrained · MANE · 24 kb · p 0.25 · regional, not allelic
Overall
CADD	19.83	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 0.0495% South Asian · 45/90,994 alleles

Filtering AF 0.0379% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0339%

Overall 0.00434% 70/1,612,986 alleles · ultra-rare exomes 68/1,460,766 · genomes 2/152,220 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0495%	2,022
European (non-Finnish)	0.00203%	49,162
Remaining individualsnot grpmax-eligible	0.0016%	62,428

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: CCDC90B
Protein: p.Ser28Pro
Coding: c.82T>C
MANE Select: NM_021825
Type: single nucleotide variant
Location: chr11:83285891 (GRCh38)
Gene constraint: LOEUF 1.112 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.37 · 1 PDB

Full CCDC90B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC90B p.Ala6Asp Uncertain significance ★ ⚠ same type
CCDC90B p.Ala6Thr Uncertain significance ★ ⚠ same type
CCDC90B p.Arg138Lys Uncertain significance ★ ⚠ same type
CCDC90B p.Arg161Gln Uncertain significance ★ ⚠ same type
CCDC90B p.Arg161Gly Uncertain significance ★ ⚠ same type
CCDC90B p.Arg163Thr Uncertain significance ★ ⚠ same type
CCDC90B p.Arg233Cys Uncertain significance ★ same type
CCDC90B p.Arg233Ser 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/ccdc90b-p-ser28pro (accessed [today's date]).

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