Is CCDC57 p.Ser180Pro (c.538T>C) pathogenic?

CCDC57 p.Ser180Pro (c.538T>C) is classified Uncertain significance in CCDC57 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-13). AlphaMissense: likely pathogenic (0.6811); Very rare (popmax 0.00239%, nfe).

How common is CCDC57 p.Ser180Pro (c.538T>C) in the general population?

CCDC57 p.Ser180Pro (c.538T>C) is very rare (popmax 0.00239%, nfe) (gnomAD).

What do computational predictors say about CCDC57 p.Ser180Pro (c.538T>C)?

AlphaMissense predicts likely pathogenic (score 0.6811) — an in-silico prediction, not a clinical call.

CCDC57 p.Ser180Pro

c.538T>C · rs767029936 · VCV2407700

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6811 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00239%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6811	likely pathogenic · top 6% in CCDC57
REVEL	0.074	moderately benign-leaning
SaProt	LLR -12.73	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -3.5, phastCons 0.039
Overall
CADD	17.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00239% European (non-Finnish) · 28/1,172,226 alleles

Filtering AF 0.00166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00143%

Overall 0.00175% 28/1,597,292 alleles · very 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: CCDC57
Protein: p.Ser180Pro
Coding: c.538T>C
MANE Select: NM_001394669
dbSNP: rs767029936
Type: single nucleotide variant
Location: chr17:82195343 (GRCh38)
Gene constraint: LOEUF 1.26 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.77
Residue 180: the 'centrosomal targeting domain' region

Full CCDC57 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC57 p.Ser180Leu Likely benign ★ same residue
CCDC57 p.Ala1009Val Uncertain significance ★ ⚠ same type
CCDC57 p.Ala222Val Uncertain significance ★ ⚠ same type
CCDC57 p.Ala231Val Uncertain significance ★ ⚠ same type
CCDC57 p.Ala329Ser Uncertain significance ★ ⚠ same type
CCDC57 p.Ala469Val Uncertain significance ★ ⚠ same type
CCDC57 p.Ala490Val Uncertain significance ★ ⚠ same type
CCDC57 p.Ala534Thr 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/ccdc57-p-ser180pro (accessed [today's date]).

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