Is CC2D1B p.Asp714Asn (c.2140G>A) pathogenic?

CC2D1B p.Asp714Asn (c.2140G>A) is classified Uncertain significance in CC2D1B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-04). AlphaMissense: likely benign (0.1002); Ultra-rare (popmax 0.0583%, amr).

How common is CC2D1B p.Asp714Asn (c.2140G>A) in the general population?

CC2D1B p.Asp714Asn (c.2140G>A) is ultra-rare (popmax 0.0583%, amr) (gnomAD).

What do computational predictors say about CC2D1B p.Asp714Asn (c.2140G>A)?

AlphaMissense predicts likely benign (score 0.1002) — an in-silico prediction, not a clinical call.

CC2D1B p.Asp714Asn

c.2140G>A · rs200283353 · VCV3138149

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1002 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0583%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1002	likely benign
REVEL	0.115	moderately benign-leaning
SaProt	LLR -6.56	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 4.8	GERP 1.9, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 11 kb · p 0.15 · regional, not allelic
Overall
CADD	21.4	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM D720N vs ClinVar D714N) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0583% Admixed American · 35/60,014 alleles

Filtering AF 0.0431% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0378%

Overall 0.00601% 97/1,614,112 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0583%	1,715
Remaining individualsnot grpmax-eligible	0.0128%	7,813
European (non-Finnish)	0.00432%	23,138
East Asian	0.00223%	44,888
Finnishnot grpmax-eligible	0.00156%	64,018
African / African-American	0.00133%	75,016

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: CC2D1B
Protein: p.Asp714Asn
Coding: c.2140G>A
MANE Select: NM_001330585
dbSNP: rs200283353
Type: single nucleotide variant
Location: chr1:52355655 (GRCh38)
Gene constraint: LOEUF 0.978 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.98
Residue 714: the c2 domain

Full CC2D1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CC2D1B p.Gly790= Benign ★★ same type
CC2D1B p.His674Tyr Likely benign ★★ same type
CC2D1B p.Leu511= Benign ★★ same type
CC2D1B p.Ala103Gly Uncertain significance ★ ⚠ same type
CC2D1B p.Ala180Ser Uncertain significance ★ ⚠ same type
CC2D1B p.Ala181Thr Uncertain significance ★ ⚠ same type
CC2D1B p.Ala181Val Uncertain significance ★ ⚠ same type
CC2D1B p.Ala208Thr 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/cc2d1b-p-asp714asn (accessed [today's date]).

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