Is CCDC38 p.Ala175Ser (c.523G>T) pathogenic?

CCDC38 p.Ala175Ser (c.523G>T) is classified Uncertain significance in CCDC38 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-12). AlphaMissense: likely benign (0.3359); Very rare (popmax 0.00415%, nfe).

How common is CCDC38 p.Ala175Ser (c.523G>T) in the general population?

CCDC38 p.Ala175Ser (c.523G>T) is very rare (popmax 0.00415%, nfe) (gnomAD).

What do computational predictors say about CCDC38 p.Ala175Ser (c.523G>T)?

AlphaMissense predicts likely benign (score 0.3359) — an in-silico prediction, not a clinical call.

CCDC38 p.Ala175Ser

c.523G>T · rs200003296 · VCV3139139

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3359 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00415%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3359	likely benign
REVEL	0.231	benign-leaning
SaProt	LLR -8.08	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 5.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 69 kb · p 0.61 · regional, not allelic
Overall
CADD	23.0	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 0.00415% European (non-Finnish) · 49/1,179,992 alleles

Filtering AF 0.00318% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00286%

Overall 0.00322% 52/1,613,952 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00415%	24,081
Admixed American	0.00333%	29,990
African / African-American	0.00134%	74,896

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.Ala175Ser
Coding: c.523G>T
MANE Select: NM_182496
dbSNP: rs200003296
Type: single nucleotide variant
Location: chr12:95898578 (GRCh38)
Gene constraint: LOEUF 0.955 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.84

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

Similar variants

CCDC38 p.Ala175Thr Uncertain significance ★ ⚠ same residue
CCDC38 p.Ala125Ser 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
CCDC38 p.Arg24Gly 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-ala175ser (accessed [today's date]).

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