Is CC2D1A p.Pro411Thr (c.1231C>A) pathogenic?

CC2D1A p.Pro411Thr (c.1231C>A) is classified Uncertain significance in CC2D1A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-09). AlphaMissense: likely benign (0.2112); Ultra-rare (popmax 0.0253%, amr).

How common is CC2D1A p.Pro411Thr (c.1231C>A) in the general population?

CC2D1A p.Pro411Thr (c.1231C>A) is ultra-rare (popmax 0.0253%, amr) (gnomAD).

What do computational predictors say about CC2D1A p.Pro411Thr (c.1231C>A)?

AlphaMissense predicts likely benign (score 0.2112) — an in-silico prediction, not a clinical call.

CC2D1A p.Pro411Thr

c.1231C>A · VCV3602942

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2112 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0253%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2112	likely benign
REVEL	0.354	indeterminate
SaProt	LLR -10.22	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.39	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 4.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 24 kb · p 0.0034 · regional, not allelic
Overall
CADD	24.2	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 0.0253% Admixed American · 15/59,378 alleles

Filtering AF 0.0155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0126%

Overall 0.00125% 20/1,602,228 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0253%	3,959
European (non-Finnish)	0.000426%	234,467

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.Pro411Thr
Coding: c.1231C>A
MANE Select: NM_017721
Type: single nucleotide variant
Location: chr19:13919826 (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

Similar variants

CC2D1A p.Pro411Ser Uncertain significance ★ ⚠ same residue
CC2D1A c.2225+1G>A Likely pathogenic ★★ same type
CC2D1A c.2454+1G>A Likely pathogenic ★★ same type
CC2D1A c.2710+1G>A Likely pathogenic ★★ same type
CC2D1A c.61-2A>G Likely pathogenic ★★ same type
CC2D1A c.748+1G>T Pathogenic ★★ same type
CC2D1A c.1941-6C>T Uncertain significance ★★ same type
CC2D1A c.2073+5G>T 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/cc2d1a-p-pro411thr (accessed [today's date]).

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