Is CCDC81 p.Tyr97= (c.291T>C) pathogenic?

CCDC81 p.Tyr97= (c.291T>C) is classified Likely benign in CCDC81 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-09). Ultra-rare (popmax 0.0137%, amr).

How common is CCDC81 p.Tyr97= (c.291T>C) in the general population?

CCDC81 p.Tyr97= (c.291T>C) is ultra-rare (popmax 0.0137%, amr) (gnomAD).

CCDC81 p.Tyr97=

c.291T>C · VCV3828816

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0137%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.26	donor loss, 6 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -0.78	GERP -5
Overall
CADD	3.541	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0137% Admixed American · 8/58,252 alleles

Filtering AF 0.00679% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00495%

Overall 0.000555% 8/1,440,766 alleles · ultra-rare

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: CCDC81
Protein: p.Tyr97=
Coding: c.291T>C
MANE Select: NM_001156474
Type: single nucleotide variant
Location: chr11:86387665 (GRCh38)
Gene constraint: LOEUF 1.125 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.04

Full CCDC81 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC81 p.Ala209Val Uncertain significance ★ ⚠ same type
CCDC81 p.Ala419Val Uncertain significance ★ ⚠ same type
CCDC81 p.Ala470Gly Uncertain significance ★ ⚠ same type
CCDC81 p.Ala53Pro Uncertain significance ★ ⚠ same type
CCDC81 p.Arg136His Uncertain significance ★ ⚠ same type
CCDC81 p.Arg157Ile Uncertain significance ★ ⚠ same type
CCDC81 p.Arg157Ser Uncertain significance ★ ⚠ same type
CCDC81 p.Arg164Thr 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/ccdc81-p-tyr97 (accessed [today's date]).

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