Is CC2D1A p.Pro320Gln (c.959C>A) pathogenic?

CC2D1A p.Pro320Gln (c.959C>A) is classified Conflicting classifications of pathogenicity in CC2D1A (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-13). AlphaMissense: likely benign (0.0764); Ultra-rare (popmax 0.0513%, eas); Associated with Inborn genetic diseases.

What condition is associated with CC2D1A p.Pro320Gln (c.959C>A)?

CC2D1A p.Pro320Gln (c.959C>A) is associated with Inborn genetic diseases (ClinVar).

How common is CC2D1A p.Pro320Gln (c.959C>A) in the general population?

CC2D1A p.Pro320Gln (c.959C>A) is ultra-rare (popmax 0.0513%, eas) (gnomAD).

What do computational predictors say about CC2D1A p.Pro320Gln (c.959C>A)?

AlphaMissense predicts likely benign (score 0.0764) — an in-silico prediction, not a clinical call.

CC2D1A p.Pro320Gln

c.959C>A · rs765282375 · VCV434598

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0764 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0513%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0764	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -7.69	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 0.21	GERP -2.6
Regional constraint	o/e 0.92	unconstrained · MANE · 24 kb · p 0.0034 · regional, not allelic
Overall
CADD	15.52	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 0.0513% East Asian · 23/44,872 alleles

Filtering AF 0.035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0296%

Overall 0.0107% 172/1,612,276 alleles · ultra-rare exomes 140/1,459,972 · genomes 32/152,304 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.35%	286
East Asiangrpmax	0.0513%	1,951
Remaining individualsnot grpmax-eligible	0.024%	4,161
Middle Eastern	0.0169%	5,922
Admixed American	0.0167%	5,985
European (non-Finnish)	0.00161%	62,061
African / African-American	0.00133%	75,040

Ashkenazi Jewish 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: CC2D1A
Protein: p.Pro320Gln
Coding: c.959C>A
MANE Select: NM_017721
dbSNP: rs765282375
Type: single nucleotide variant
Location: chr19:13918758 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.71 · 1 PDB
Residue 320: the 'disordered' region

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 p.Pro320Arg Uncertain significance ★ ⚠ same residue
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

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-pro320gln (accessed [today's date]).

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