Is CCDC57 p.Arg89Trp (c.265C>T) pathogenic?

CCDC57 p.Arg89Trp (c.265C>T) is classified Uncertain significance in CCDC57 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-15). AlphaMissense: likely benign (0.1218); Ultra-rare (popmax 0.05%, amr).

How common is CCDC57 p.Arg89Trp (c.265C>T) in the general population?

CCDC57 p.Arg89Trp (c.265C>T) is ultra-rare (popmax 0.05%, amr) (gnomAD).

What do computational predictors say about CCDC57 p.Arg89Trp (c.265C>T)?

AlphaMissense predicts likely benign (score 0.1218) — an in-silico prediction, not a clinical call.

CCDC57 p.Arg89Trp

c.265C>T · rs759931984 · VCV2364673

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1218 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.05%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1218	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -10.17	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP 3.5, phastCons 1
Overall
CADD	26.8	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 0.05% Admixed American · 30/59,992 alleles

Filtering AF 0.0359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0312%

Overall 0.00273% 44/1,613,156 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.05%	2,000
Remaining individualsnot grpmax-eligible	0.00641%	15,605
European (non-Finnish)	0.000848%	117,936

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.Arg89Trp
Coding: c.265C>T
MANE Select: NM_001394669
dbSNP: rs759931984
Type: single nucleotide variant
Location: chr17:82201680 (GRCh38)
Gene constraint: LOEUF 1.26 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.77
Residue 89: the 'centrosomal targeting domain' region

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

Similar variants

CCDC57 p.Arg89Gln 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-arg89trp (accessed [today's date]).

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