Is CCDC150 p.Ile685Val (c.2053A>G) pathogenic?

CCDC150 p.Ile685Val (c.2053A>G) is classified Uncertain significance in CCDC150 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-21). AlphaMissense: likely benign (0.063); Very rare (popmax 0.0022%, sas).

How common is CCDC150 p.Ile685Val (c.2053A>G) in the general population?

CCDC150 p.Ile685Val (c.2053A>G) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about CCDC150 p.Ile685Val (c.2053A>G)?

AlphaMissense predicts likely benign (score 0.063) — an in-silico prediction, not a clinical call.

CCDC150 p.Ile685Val

c.2053A>G · VCV4220687

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.063 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.063	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -5.60	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 -0.47	GERP -0.61
Regional constraint	o/e 1.03	unconstrained · MANE · 93 kb · p 0.22 · regional, not allelic
Overall
CADD	10.73	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 0.0022% South Asian · 2/90,852 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000806% 13/1,612,822 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,426
Finnishnot grpmax-eligible	0.00156%	63,994
European (non-Finnish)	0.000848%	117,941

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.Ile685Val
Coding: c.2053A>G
MANE Select: NM_001080539
Type: single nucleotide variant
Location: chr2:196719554 (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-ile685val (accessed [today's date]).

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