Is CCDC149 p.Asp92Gly (c.275A>G) pathogenic?

CCDC149 p.Asp92Gly (c.275A>G) is classified Uncertain significance in CCDC149 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-16). Very rare (popmax 8.48e-05%, nfe).

How common is CCDC149 p.Asp92Gly (c.275A>G) in the general population?

CCDC149 p.Asp92Gly (c.275A>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

CCDC149 p.Asp92Gly

c.275A>G · rs1158875731 · VCV2326161

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.312	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 104 kb · p 0.0018 · regional, not allelic
Overall
CADD	26.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,178,892 alleles

Overall 0.00031% 5/1,612,690 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00625%	15,988
European (non-Finnish)grpmax	8.48e-05%	1,178,892

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp92Gly
Coding: c.275A>G
MANE Select: NM_001395273
dbSNP: rs1158875731
Type: single nucleotide variant
Location: chr4:24853154 (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-asp92gly (accessed [today's date]).

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