Is ANKRD36 p.Asp404= (c.1212C>T) pathogenic?

ANKRD36 p.Asp404= (c.1212C>T) is classified Likely benign in ANKRD36 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-01). Rare (popmax 0.169%, afr).

How common is ANKRD36 p.Asp404= (c.1212C>T) in the general population?

ANKRD36 p.Asp404= (c.1212C>T) is rare (popmax 0.169%, afr) (gnomAD).

ANKRD36 p.Asp404=

c.1212C>T · rs776281681 · VCV2651160

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.169%, afr)

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 -1.3
Overall
CADD	0.427	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.169% African / African-American · 95/56,304 alleles

Filtering AF 0.141% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.131%

Overall 0.0499% 706/1,413,536 alleles · rare exomes 83/1,321,826 · genomes 623/91,710 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.542%	185
Finnishnot grpmax-eligible	0.32%	312
African / African-Americangrpmax	0.169%	593
Admixed American	0.151%	663
East Asian	0.0688%	1,453
Middle Eastern	0.0346%	2,892
Ashkenazi Jewishnot grpmax-eligible	0.0338%	2,958
European (non-Finnish)	0.0338%	2,961
South Asian	0.0251%	3,980
Remaining individualsnot grpmax-eligible	0.0194%	5,161

Amish 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: ANKRD36
Protein: p.Asp404=
Coding: c.1212C>T
MANE Select: NM_001354587
dbSNP: rs776281681
Type: single nucleotide variant
Location: chr2:97154693 (GRCh38)
Gene constraint: LOEUF 1.132 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.82

Full ANKRD36 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD36 c.2173-3A>C Likely benign ★ same type
ANKRD36 c.-4G>C Likely benign ★ same type
ANKRD36 p.Ala228= Likely benign ★ same type
ANKRD36 p.Asp558= Likely benign ★ same type
ANKRD36 p.Cys1792= Likely benign ★ same type
ANKRD36 p.Cys445= Likely benign ★ same type
ANKRD36 p.Gly1189= Likely benign ★ same type
ANKRD36 p.Gly295= Likely benign ★ 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/ankrd36-p-asp404 (accessed [today's date]).

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