Is CEP89 p.Asp381= (c.1143C>T) pathogenic?

CEP89 p.Asp381= (c.1143C>T) is classified Likely benign in CEP89 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-30). Ultra-rare (popmax 0.0987%, mid).

How common is CEP89 p.Asp381= (c.1143C>T) in the general population?

CEP89 p.Asp381= (c.1143C>T) is ultra-rare (popmax 0.0987%, mid) (gnomAD).

CEP89 p.Asp381=

c.1143C>T · rs148166691 · VCV2720121

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0987%, mid)

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 -5	GERP -3.7
Overall
CADD	1.778	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0987% Middle Eastern · 6/6,080 alleles

Filtering AF 0.0429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0293%

Overall 0.008% 129/1,613,206 alleles · ultra-rare exomes 119/1,461,090 · genomes 10/152,116 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0987%	1,013
Remaining individualsnot grpmax-eligible	0.016%	6,246
European (non-Finnish)	0.00916%	10,921
Admixed American	0.00333%	29,988
African / African-American	0.00267%	37,436
South Asian	0.0011%	91,060

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: CEP89
Protein: p.Asp381=
Coding: c.1143C>T
MANE Select: NM_032816
dbSNP: rs148166691
Type: single nucleotide variant
Location: chr19:32926211 (GRCh38)
Gene constraint: LOEUF 1.173 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.08

Full CEP89 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP89 p.Ala291Thr Uncertain significance ★★ ⚠ same type
CEP89 p.Ala291Val Uncertain significance ★★ ⚠ same type
CEP89 p.Ala372Thr Uncertain significance ★★ ⚠ same type
CEP89 p.Ala54Val Uncertain significance ★★ ⚠ same type
CEP89 p.Ala680Thr Uncertain significance ★★ ⚠ same type
CEP89 p.Ala780Asp Uncertain significance ★★ ⚠ same type
CEP89 p.Arg102Trp Uncertain significance ★★ ⚠ same type
CEP89 p.Arg324Cys 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/cep89-p-asp381 (accessed [today's date]).

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