Is CCDC81 p.Pro403Leu (c.1208C>T) pathogenic?

CCDC81 p.Pro403Leu (c.1208C>T) is classified Uncertain significance in CCDC81 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-22). AlphaMissense: likely benign (0.1555); Very rare (popmax 0.00399%, sas).

How common is CCDC81 p.Pro403Leu (c.1208C>T) in the general population?

CCDC81 p.Pro403Leu (c.1208C>T) is very rare (popmax 0.00399%, sas) (gnomAD).

What do computational predictors say about CCDC81 p.Pro403Leu (c.1208C>T)?

AlphaMissense predicts likely benign (score 0.1555) — an in-silico prediction, not a clinical call.

CCDC81 p.Pro403Leu

c.1208C>T · VCV3264323

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1555 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00399%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1555	likely benign
REVEL	0.18	moderately benign-leaning
SaProt	LLR -8.14	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 4.9	GERP 0.98, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 48 kb · p 0.64 · regional, not allelic
Overall
CADD	24.2	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

Grpmax group 0.00399% South Asian · 3/75,146 alleles

Filtering AF 0.0012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00102%

Overall 0.00179% 27/1,506,834 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00399%	25,049
East Asian	0.00251%	39,886
European (non-Finnish)	0.00187%	53,609
Finnishnot grpmax-eligible	0.00162%	61,780
African / African-American	0.00144%	69,524

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.Pro403Leu
Coding: c.1208C>T
MANE Select: NM_001156474
Type: single nucleotide variant
Location: chr11:86409355 (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-pro403leu (accessed [today's date]).

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