Is CC2D2B p.Leu89= (c.265T>C) pathogenic?

CC2D2B p.Leu89= (c.265T>C) is classified Likely benign in CC2D2B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-01). Ultra-rare (popmax 0.0742%, nfe).

How common is CC2D2B p.Leu89= (c.265T>C) in the general population?

CC2D2B p.Leu89= (c.265T>C) is ultra-rare (popmax 0.0742%, nfe) (gnomAD).

CC2D2B p.Leu89=

c.265T>C · rs201173034 · VCV2640721

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0742%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.6	GERP -5.1
Overall
CADD	0.304	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0742% European (non-Finnish) · 850/1,144,966 alleles

Filtering AF 0.0701% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0684%

Overall 0.105% 1,625/1,549,768 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.2%	83
European (non-Finnish)grpmax	0.0742%	1,347
Remaining individualsnot grpmax-eligible	0.0631%	1,584
Middle Eastern	0.0167%	5,994
Admixed American	0.00785%	12,745
African / African-American	0.00547%	18,270
South Asian	0.00476%	20,990
East Asian	0.00244%	40,908

Finnish 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: CC2D2B
Protein: p.Leu89=
Coding: c.265T>C
MANE Select: NM_001349008
dbSNP: rs201173034
Type: single nucleotide variant
Location: chr10:95927261 (GRCh38)
Gene constraint: LOEUF 0.832 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.49

Full CC2D2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CC2D2B p.Arg1101Gln Uncertain significance ★ ⚠ same type
CC2D2B p.Arg1329Gln Uncertain significance ★ ⚠ same type
CC2D2B p.Arg1345Pro Uncertain significance ★ ⚠ same type
CC2D2B p.Asn1422Ser Uncertain significance ★ ⚠ same type
CC2D2B p.Asp1248Asn Uncertain significance ★ ⚠ same type
CC2D2B p.Asp1312Glu Uncertain significance ★ ⚠ same type
CC2D2B p.Cys1234Arg Uncertain significance ★ ⚠ same type
CC2D2B p.Cys985Tyr 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/cc2d2b-p-leu89 (accessed [today's date]).

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