Is CCDC148 p.Arg298Ser (c.894G>T) pathogenic?

CCDC148 p.Arg298Ser (c.894G>T) is classified Uncertain significance in CCDC148 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-30). AlphaMissense: likely pathogenic (0.7607); Very rare (popmax 8.48e-05%, nfe).

How common is CCDC148 p.Arg298Ser (c.894G>T) in the general population?

CCDC148 p.Arg298Ser (c.894G>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CCDC148 p.Arg298Ser (c.894G>T)?

AlphaMissense predicts likely pathogenic (score 0.7607) — an in-silico prediction, not a clinical call.

CCDC148 p.Arg298Ser

c.894G>T · rs2467977467 · VCV3138490

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7607 · ACMG-weighted

gnomAD v4.1

Rare

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

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7607	likely pathogenic · top 4% in CCDC148
REVEL	0.247	benign-leaning
SaProt	LLR -11.19	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.11	GERP -0.53, phastCons 0.92
Regional constraint	o/e 1.03	unconstrained · MANE · 284 kb · p 0.43 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,666 alleles

Overall 6.84e-05% 1/1,461,104 alleles · very rare

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: CCDC148
Protein: p.Arg298Ser
Coding: c.894G>T
MANE Select: NM_138803
dbSNP: rs2467977467
Type: single nucleotide variant
Location: chr2:158313765 (GRCh38)
Gene constraint: LOEUF 1.209 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.14

Full CCDC148 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC148 p.Gln75Pro Benign ★★ ⚠ same type
CCDC148 p.Glu387= Benign ★★ same type
CCDC148 p.Glu522Lys Benign ★★ same type
CCDC148 p.Tyr307Phe Benign ★★ same type
CCDC148 p.Ala135Thr Uncertain significance ★ ⚠ same type
CCDC148 p.Ala42Pro Uncertain significance ★ ⚠ same type
CCDC148 p.Ala448Ser Uncertain significance ★ ⚠ same type
CCDC148 p.Ala448Thr 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/ccdc148-p-arg298ser (accessed [today's date]).

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