Is CCDC149 p.Asp503Tyr (c.1507G>T) pathogenic?

CCDC149 p.Asp503Tyr (c.1507G>T) is classified Uncertain significance in CCDC149 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-10). Very rare (popmax 0.00568%, nfe).

How common is CCDC149 p.Asp503Tyr (c.1507G>T) in the general population?

CCDC149 p.Asp503Tyr (c.1507G>T) is very rare (popmax 0.00568%, nfe) (gnomAD).

CCDC149 p.Asp503Tyr

c.1507G>T · VCV3486105

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00568%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.112	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.35	GERP -0.51, phastCons 0.001
Regional constraint	o/e 0.88	unconstrained · MANE · 104 kb · p 0.0018 · regional, not allelic
Overall
CADD	14.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00568% European (non-Finnish) · 64/1,126,430 alleles

Filtering AF 0.00455% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00414%

Overall 0.00446% 67/1,502,718 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00568%	17,600
Remaining individualsnot grpmax-eligible	0.00518%	19,305

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: CCDC149
Protein: p.Asp503Tyr
Coding: c.1507G>T
MANE Select: NM_001395273
Type: single nucleotide variant
Location: chr4:24808490 (GRCh38)
Gene constraint: LOEUF 1.15 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.52

Full CCDC149 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC149 c.48+17788T>A Uncertain significance ★ same type
CCDC149 c.48+17796A>G Uncertain significance ★ same type
CCDC149 c.48+17799G>A Uncertain significance ★ same type
CCDC149 c.48+17811A>T Uncertain significance ★ same type
CCDC149 p.Ala412Val Uncertain significance ★ same type
CCDC149 p.Ala420Thr Uncertain significance ★ same type
CCDC149 p.Arg110Ser Uncertain significance ★ same type
CCDC149 p.Arg145His 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/ccdc149-p-asp503tyr (accessed [today's date]).

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