Is CCDC149 p.Thr484Met (c.1451C>T) pathogenic?

CCDC149 p.Thr484Met (c.1451C>T) is classified Likely benign in CCDC149 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-08). Ultra-rare (popmax 0.0334%, mid).

How common is CCDC149 p.Thr484Met (c.1451C>T) in the general population?

CCDC149 p.Thr484Met (c.1451C>T) is ultra-rare (popmax 0.0334%, mid) (gnomAD).

CCDC149 p.Thr484Met

c.1451C>T · VCV3996564

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0334%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.008	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.9	GERP -3.2
Regional constraint	o/e 0.88	unconstrained · MANE · 104 kb · p 0.0018 · regional, not allelic
Overall
CADD	0.094	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0334% Middle Eastern · 2/5,982 alleles

Filtering AF 0.0187% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0158%

Overall 0.00265% 41/1,549,870 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0334%	2,991
South Asian	0.0274%	3,644
East Asian	0.00245%	40,884
Finnishnot grpmax-eligible	0.00167%	59,846
African / African-American	0.00137%	73,024
European (non-Finnish)	0.00113%	88,155

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.Thr484Met
Coding: c.1451C>T
MANE Select: NM_001395273
Type: single nucleotide variant
Location: chr4:24808546 (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-thr484met (accessed [today's date]).

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