Is CCDC159 p.Cys250Arg (c.748T>C) pathogenic?

CCDC159 p.Cys250Arg (c.748T>C) is classified Likely benign in CCDC159 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-05). AlphaMissense: likely benign (0.0447); Very rare (popmax 0.00358%, amr).

How common is CCDC159 p.Cys250Arg (c.748T>C) in the general population?

CCDC159 p.Cys250Arg (c.748T>C) is very rare (popmax 0.00358%, amr) (gnomAD).

What do computational predictors say about CCDC159 p.Cys250Arg (c.748T>C)?

AlphaMissense predicts likely benign (score 0.0447) — an in-silico prediction, not a clinical call.

CCDC159 p.Cys250Arg

c.748T>C · rs1315157173 · VCV2406711

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0447 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00358%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0447	likely benign
REVEL	0.01	strongly benign-leaning
SaProt	LLR -5.34	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 -0.51	GERP -4.8
Regional constraint	o/e 0.96	unconstrained · MANE · 8,267 bp · p 0.42 · regional, not allelic
Overall
CADD	0.053	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 0.00358% Admixed American · 2/55,790 alleles

Filtering AF 0.000595% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000223%

Overall 0.000315% 5/1,588,380 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00358%	27,895
European (non-Finnish)	0.000257%	389,238

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: CCDC159
Protein: p.Cys250Arg
Coding: c.748T>C
MANE Select: NM_001080503
dbSNP: rs1315157173
Type: single nucleotide variant
Location: chr19:11353850 (GRCh38)
Gene constraint: LOEUF 1.11 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.97

Full CCDC159 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC159 p.Ala203Thr Uncertain significance ★ ⚠ same type
CCDC159 p.Ala45Asp Uncertain significance ★ ⚠ same type
CCDC159 p.Arg117Cys Uncertain significance ★ ⚠ same type
CCDC159 p.Arg117His Uncertain significance ★ ⚠ same type
CCDC159 p.Arg124Trp Uncertain significance ★ ⚠ same type
CCDC159 p.Arg126Gly Uncertain significance ★ ⚠ same type
CCDC159 p.Arg139Gln Uncertain significance ★ ⚠ same type
CCDC159 p.Arg139Trp 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/ccdc159-p-cys250arg (accessed [today's date]).

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