Is CCDC149 p.Ala409Val (c.1226C>T) pathogenic?

CCDC149 p.Ala409Val (c.1226C>T) is classified Likely benign in CCDC149 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-27). Ultra-rare (popmax 0.022%, eas).

How common is CCDC149 p.Ala409Val (c.1226C>T) in the general population?

CCDC149 p.Ala409Val (c.1226C>T) is ultra-rare (popmax 0.022%, eas) (gnomAD).

CCDC149 p.Ala409Val

c.1226C>T · rs556415780 · VCV3138493

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.022%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type.
REVEL	0.069	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Regional constraint	o/e 0.88	unconstrained · MANE · 104 kb · p 0.0018 · regional, not allelic
Overall
CADD	8.522	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.022% East Asian · 9/40,900 alleles

Filtering AF 0.0114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00855%

Overall 0.00122% 19/1,551,358 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.022%	4,544
Ashkenazi Jewishnot grpmax-eligible	0.00349%	28,618
Admixed American	0.00197%	50,874
European (non-Finnish)	0.000698%	143,362

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.Ala409Val
Coding: c.1226C>T
MANE Select: NM_001395273
dbSNP: rs556415780
Type: single nucleotide variant
Location: chr4:24808771 (GRCh38)
Gene constraint: LOEUF 1.15 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.52
Residue 409: the 'disordered' region

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-ala409val (accessed [today's date]).

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