Is CCDC91 p.Ala28Ser (c.82G>T) pathogenic?

CCDC91 p.Ala28Ser (c.82G>T) is classified Uncertain significance in CCDC91 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-27). AlphaMissense: likely benign (0.3294); Absent from gnomAD v4.1.

How common is CCDC91 p.Ala28Ser (c.82G>T) in the general population?

CCDC91 p.Ala28Ser (c.82G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCDC91 p.Ala28Ser (c.82G>T)?

AlphaMissense predicts likely benign (score 0.3294) — an in-silico prediction, not a clinical call.

CCDC91 p.Ala28Ser

c.82G>T · VCV3997390

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3294 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3294	likely benign
REVEL	0.195	benign-leaning
SaProt	LLR -5.31	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 12	GERP 1.6, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 292 kb · p 0.81 · regional, not allelic
Overall
CADD	26.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CCDC91
Protein: p.Ala28Ser
Coding: c.82G>T
MANE Select: NM_018318
Type: single nucleotide variant
Location: chr12:28259415 (GRCh38)
Gene constraint: LOEUF 1.084 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 76.04 · 1 PDB

Full CCDC91 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC91 p.Asp121Gly Benign ★★ same type
CCDC91 p.Gln403Lys Benign ★★ same type
CCDC91 p.Ala127Thr Uncertain significance ★ ⚠ same type
CCDC91 p.Ala181Thr Uncertain significance ★ ⚠ same type
CCDC91 p.Ala209Thr Uncertain significance ★ ⚠ same type
CCDC91 p.Ala219Thr Uncertain significance ★ ⚠ same type
CCDC91 p.Ala334Gly Uncertain significance ★ ⚠ same type
CCDC91 p.Ala36Glu 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/ccdc91-p-ala28ser (accessed [today's date]).

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