Is CCDC38 p.Ser306Pro (c.916T>C) pathogenic?

CCDC38 p.Ser306Pro (c.916T>C) is classified Uncertain significance in CCDC38 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-02). AlphaMissense: likely benign (0.0759); Very rare (popmax 0.00167%, amr).

How common is CCDC38 p.Ser306Pro (c.916T>C) in the general population?

CCDC38 p.Ser306Pro (c.916T>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CCDC38 p.Ser306Pro (c.916T>C)?

AlphaMissense predicts likely benign (score 0.0759) — an in-silico prediction, not a clinical call.

CCDC38 p.Ser306Pro

c.916T>C · VCV4649506

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0759 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0759	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -7.22	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 0.49	GERP 1.5, phastCons 0.002
Regional constraint	o/e 0.98	unconstrained · MANE · 69 kb · p 0.61 · regional, not allelic
Overall
CADD	9.987	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 0.00167% Admixed American · 1/60,000 alleles

Overall 0.000186% 3/1,613,924 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,000
Remaining individualsnot grpmax-eligible	0.0016%	62,498
African / African-American	0.00133%	74,984

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: CCDC38
Protein: p.Ser306Pro
Coding: c.916T>C
MANE Select: NM_182496
Type: single nucleotide variant
Location: chr12:95888462 (GRCh38)
Gene constraint: LOEUF 0.955 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.84
Residue 306: the 'disordered' region

Full CCDC38 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC38 p.Ala125Ser Uncertain significance ★ ⚠ same type
CCDC38 p.Ala175Ser Uncertain significance ★ ⚠ same type
CCDC38 p.Ala175Thr Uncertain significance ★ ⚠ same type
CCDC38 p.Ala407Val Uncertain significance ★ ⚠ same type
CCDC38 p.Ala425Val Uncertain significance ★ ⚠ same type
CCDC38 p.Ala76Pro Uncertain significance ★ ⚠ same type
CCDC38 p.Arg107Met Uncertain significance ★ ⚠ same type
CCDC38 p.Arg145Gln 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/ccdc38-p-ser306pro (accessed [today's date]).

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