Is CC2D1A p.Pro650Ser (c.1948C>T) pathogenic?

CC2D1A p.Pro650Ser (c.1948C>T) is classified Uncertain significance in CC2D1A (ClinVar, Single submitter, 2 submitters; last evaluated 2019-05-30). AlphaMissense: likely benign (0.0956); Very rare (popmax 0.00446%, eas); Associated with intellectual disability, autosomal recessive 3.

What condition is associated with CC2D1A p.Pro650Ser (c.1948C>T)?

CC2D1A p.Pro650Ser (c.1948C>T) is associated with intellectual disability, autosomal recessive 3 (ClinVar).

How common is CC2D1A p.Pro650Ser (c.1948C>T) in the general population?

CC2D1A p.Pro650Ser (c.1948C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about CC2D1A p.Pro650Ser (c.1948C>T)?

AlphaMissense predicts likely benign (score 0.0956) — an in-silico prediction, not a clinical call.

CC2D1A p.Pro650Ser

c.1948C>T · rs746894472 · VCV1030586

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0956 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability, autosomal recessive 3

Computational evidence

Protein change
AlphaMissense	0.0956	likely benign
REVEL	0.088	moderately benign-leaning
SaProt	LLR -7.55	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.25	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 4	GERP -3.6, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 24 kb · p 0.0034 · regional, not allelic
Overall
CADD	22.9	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 0.00446% East Asian · 2/44,876 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000186% 3/1,613,908 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,438
Admixed American	0.00167%	59,972

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.Pro650Ser
Coding: c.1948C>T
MANE Select: NM_017721
dbSNP: rs746894472
Type: single nucleotide variant
Location: chr19:13926524 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.71 · 1 PDB
Residue 650: the c2 domain

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

Disease context

intellectual disability, autosomal recessive 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CC2D1A c.2225+1G>A Likely pathogenic ★★ same condition
CC2D1A c.2454+1G>A Likely pathogenic ★★ same condition
CC2D1A c.2710+1G>A Likely pathogenic ★★ same condition
CC2D1A c.61-2A>G Likely pathogenic ★★ same condition
CC2D1A c.748+1G>T Pathogenic ★★ same condition
CC2D1A c.2073+5G>T Uncertain significance ★★ same condition
CC2D1A p.Ala154Thr Uncertain significance ★★ ⚠ same condition
CC2D1A p.Ala481Val 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-pro650ser (accessed [today's date]).

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