Is CC2D1A p.Ala50Ser (c.148G>T) pathogenic?

CC2D1A p.Ala50Ser (c.148G>T) is classified Uncertain significance in CC2D1A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-06-27). AlphaMissense: likely benign (0.1049); Ultra-rare (popmax 0.052%, mid); Associated with Inborn genetic diseases.

What condition is associated with CC2D1A p.Ala50Ser (c.148G>T)?

CC2D1A p.Ala50Ser (c.148G>T) is associated with Inborn genetic diseases (ClinVar).

How common is CC2D1A p.Ala50Ser (c.148G>T) in the general population?

CC2D1A p.Ala50Ser (c.148G>T) is ultra-rare (popmax 0.052%, mid) (gnomAD).

What do computational predictors say about CC2D1A p.Ala50Ser (c.148G>T)?

AlphaMissense predicts likely benign (score 0.1049) — an in-silico prediction, not a clinical call.

CC2D1A p.Ala50Ser

c.148G>T · rs368933699 · VCV589401

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1049 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.052%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1049	likely benign
REVEL	0.096	moderately benign-leaning
SaProt	LLR -6.87	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 24 kb · p 0.0034 · regional, not allelic
Overall
CADD	20.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.052% Middle Eastern · 3/5,768 alleles

Filtering AF 0.0141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00754%

Overall 0.00787% 122/1,549,742 alleles · ultra-rare exomes 116/1,397,558 · genomes 6/152,184 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.052%	1,923
Remaining individualsnot grpmax-eligible	0.0151%	6,630
European (non-Finnish)	0.00863%	11,585
Admixed American	0.00789%	12,673
African / African-American	0.00687%	14,565
South Asian	0.00246%	40,685

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: CC2D1A
Protein: p.Ala50Ser
Coding: c.148G>T
MANE Select: NM_017721
dbSNP: rs368933699
Type: single nucleotide variant
Location: chr19:13909910 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.71 · 1 PDB

Full CC2D1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CC2D1A c.61-2A>G Likely pathogenic ★★ same condition
CC2D1A c.1941-6C>T Uncertain significance ★★ same condition
CC2D1A c.2073+5G>T Uncertain significance ★★ same condition
CC2D1A c.946+6A>G Uncertain significance ★★ same condition
CC2D1A p.Ala154Thr Uncertain significance ★★ ⚠ same condition
CC2D1A p.Ala481Val Uncertain significance ★★ ⚠ same condition
CC2D1A p.Ala507Val Uncertain significance ★★ ⚠ same condition
CC2D1A p.Ala613Val Uncertain significance ★★ ⚠ same condition

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/cc2d1a-p-ala50ser (accessed [today's date]).

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