Is ANAPC15 p.Asp72= (c.216T>C) pathogenic?

ANAPC15 p.Asp72= (c.216T>C) is classified Likely benign in ANAPC15 (ClinVar, Single submitter, 1 submitter). Common (popmax 22.6%, eas) — too common for a highly-penetrant pathogenic allele.

ANAPC15 p.Asp72=

Q: How common is ANAPC15 p.Asp72= (c.216T>C) in the general population?

ANAPC15 p.Asp72= (c.216T>C) is common (popmax 22.6%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.216T>C · rs17161980 · VCV306015

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 22.6%, eas) — too common for a highly-penetrant pathogenic allele

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 -8.6	GERP -3.8
Overall
CADD	0.067	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 22.6% East Asian · 10,124/44,832 alleles

Filtering AF 22.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 22.1%

Overall 7.51% 121,219/1,613,710 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	22.6%	4
African / African-American	18.7%	5
South Asian	15.6%	6
Admixed American	15.1%	7
Ashkenazi Jewishnot grpmax-eligible	9%	11
Remaining individualsnot grpmax-eligible	8.35%	12
Middle Eastern	8.33%	12
Finnishnot grpmax-eligible	6.98%	14
Amishnot grpmax-eligible	5.74%	17
European (non-Finnish)	5.17%	19

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: ANAPC15
Protein: p.Asp72=
Coding: c.216T>C
MANE Select: NM_014042
dbSNP: rs17161980
Type: single nucleotide variant
Location: chr11:72110190 (GRCh38)
Gene constraint: LOEUF 0.939 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 71.01 · 18 PDB
Residue 72: the 'disordered' region

Full ANAPC15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANAPC15 p.Asp72Tyr Uncertain significance ★ ⚠ same residue
LRTOMT p.Ala133Thr Uncertain significance ★★ ⚠ same type
LRTOMT p.Ala250Val Uncertain significance ★★ same type
LRTOMT p.Arg125Gln Uncertain significance ★★ ⚠ same type
LRTOMT p.Arg125Trp Uncertain significance ★★ same type
LRTOMT p.Arg164Gln Uncertain significance ★★ ⚠ same type
LRTOMT p.Arg167Cys Uncertain significance ★★ ⚠ same type
LRTOMT p.Arg217Gln 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/anapc15-p-asp72 (accessed [today's date]).

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