Is CCDC13 p.Phe122Tyr (c.365T>A) pathogenic?

CCDC13 p.Phe122Tyr (c.365T>A) is classified Uncertain significance in CCDC13 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: likely benign (0.2529); Ultra-rare (popmax 0.0725%, sas).

How common is CCDC13 p.Phe122Tyr (c.365T>A) in the general population?

CCDC13 p.Phe122Tyr (c.365T>A) is ultra-rare (popmax 0.0725%, sas) (gnomAD).

What do computational predictors say about CCDC13 p.Phe122Tyr (c.365T>A)?

AlphaMissense predicts likely benign (score 0.2529) — an in-silico prediction, not a clinical call.

CCDC13 p.Phe122Tyr

c.365T>A · VCV4648999

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2529 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0725%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2529	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -6.52	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 11	GERP 2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 49 kb · p 0.094 · regional, not allelic
Overall
CADD	26.3	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 0.0725% South Asian · 66/91,026 alleles

Filtering AF 0.0584% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0533%

Overall 0.00533% 86/1,613,782 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0725%	1,379
Middle Eastern	0.0165%	6,058
Remaining individualsnot grpmax-eligible	0.0032%	31,244
African / African-American	0.00266%	37,526
European (non-Finnish)	0.00127%	78,652

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: CCDC13
Protein: p.Phe122Tyr
Coding: c.365T>A
MANE Select: NM_144719
Type: single nucleotide variant
Location: chr3:42757071 (GRCh38)
Gene constraint: LOEUF 0.906 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.77

Full CCDC13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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CCDC13 p.Ala187Thr Uncertain significance ★ ⚠ same type
CCDC13 p.Ala332Gly Uncertain significance ★ ⚠ same type
CCDC13 p.Ala3Val Uncertain significance ★ ⚠ same type
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CCDC13 p.Ala544Thr 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/ccdc13-p-phe122tyr (accessed [today's date]).

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