Is CCDC150 p.Arg641Cys (c.1921C>T) pathogenic?

CCDC150 p.Arg641Cys (c.1921C>T) is classified Uncertain significance in CCDC150 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-24). AlphaMissense: likely benign (0.1296); Very rare (popmax 0.00669%, eas).

How common is CCDC150 p.Arg641Cys (c.1921C>T) in the general population?

CCDC150 p.Arg641Cys (c.1921C>T) is very rare (popmax 0.00669%, eas) (gnomAD).

What do computational predictors say about CCDC150 p.Arg641Cys (c.1921C>T)?

AlphaMissense predicts likely benign (score 0.1296) — an in-silico prediction, not a clinical call.

CCDC150 p.Arg641Cys

c.1921C>T · rs138410566 · VCV3138529

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1296 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1296	likely benign
REVEL	0.14	moderately benign-leaning
SaProt	LLR -8.83	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 3.8	GERP 1.9, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 93 kb · p 0.22 · regional, not allelic
Overall
CADD	22.7	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 0.00669% East Asian · 3/44,870 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000558% 9/1,613,624 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,957
South Asian	0.0022%	45,497
Remaining individualsnot grpmax-eligible	0.0016%	62,470
African / African-American	0.00133%	75,016
European (non-Finnish)	0.00017%	589,859

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: CCDC150
Protein: p.Arg641Cys
Coding: c.1921C>T
MANE Select: NM_001080539
dbSNP: rs138410566
Type: single nucleotide variant
Location: chr2:196718557 (GRCh38)
Gene constraint: LOEUF 1.112 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.19

Full CCDC150 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC150 p.Ala166Ser Uncertain significance ★ ⚠ same type
CCDC150 p.Ala166Thr Uncertain significance ★ ⚠ same type
CCDC150 p.Ala183Ser Uncertain significance ★ ⚠ same type
CCDC150 p.Ala419Glu Uncertain significance ★ ⚠ same type
CCDC150 p.Ala438Val Uncertain significance ★ ⚠ same type
CCDC150 p.Ala443Thr Uncertain significance ★ ⚠ same type
CCDC150 p.Ala454Pro Uncertain significance ★ ⚠ same type
CCDC150 p.Ala462Thr 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/ccdc150-p-arg641cys (accessed [today's date]).

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