Is CCDC148 p.Gln75Pro (c.224A>C) pathogenic?

CCDC148 p.Gln75Pro (c.224A>C) is classified Benign in CCDC148 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). AlphaMissense: ambiguous (0.4339); Low-frequency (popmax 2.21%, afr).

How common is CCDC148 p.Gln75Pro (c.224A>C) in the general population?

CCDC148 p.Gln75Pro (c.224A>C) is low-frequency (popmax 2.21%, afr) (gnomAD).

What do computational predictors say about CCDC148 p.Gln75Pro (c.224A>C)?

AlphaMissense predicts ambiguous (score 0.4339) — an in-silico prediction, not a clinical call.

CCDC148 p.Gln75Pro

c.224A>C · rs4664950 · VCV777565

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4339 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.21%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4339	ambiguous
REVEL	0.221	benign-leaning
SaProt	LLR -12.76	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP 1.6, phastCons 0.99
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 2.21% African / African-American · 1,656/75,018 alleles

Filtering AF 2.12% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.08%

Overall 0.114% 1,847/1,613,514 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.21%	45
Remaining individualsnot grpmax-eligible	0.138%	726
Admixed American	0.112%	895
Middle Eastern	0.0165%	6,056
South Asian	0.0033%	30,345
European (non-Finnish)	0.00288%	34,696

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.Gln75Pro
Coding: c.224A>C
MANE Select: NM_138803
dbSNP: rs4664950
Type: single nucleotide variant
Location: chr2:158345242 (GRCh38)
Gene constraint: LOEUF 1.209 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.14
Residue 75: a UniProt-annotated variant site (in)

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

Similar variants

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
CCDC148 p.Ala46Val 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-gln75pro (accessed [today's date]).

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