Is ANKRD36C p.Ser955= (c.2865T>A) pathogenic?

ANKRD36C p.Ser955= (c.2865T>A) is classified Likely benign in ANKRD36C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-01). Ultra-rare (popmax 0.0763%, amr).

How common is ANKRD36C p.Ser955= (c.2865T>A) in the general population?

ANKRD36C p.Ser955= (c.2865T>A) is ultra-rare (popmax 0.0763%, amr) (gnomAD).

ANKRD36C p.Ser955=

c.2865T>A · rs183934154 · VCV2651130

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0763%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.18	GERP 1.4
Overall
CADD	1.26	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0763% Admixed American · 40/52,440 alleles

Filtering AF 0.0576% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.051%

Overall 0.0478% 743/1,553,520 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.169%	593
Ashkenazi Jewishnot grpmax-eligible	0.0773%	1,293
Admixed Americangrpmax	0.0763%	1,311
Remaining individualsnot grpmax-eligible	0.0451%	2,218
European (non-Finnish)	0.0437%	2,290
South Asian	0.0307%	3,257
African / African-American	0.0273%	3,657
Middle Eastern	0.0233%	4,294
East Asian	0.00953%	10,491

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: ANKRD36C
Protein: p.Ser955=
Coding: c.2865T>A
MANE Select: NM_001393982
dbSNP: rs183934154
Type: single nucleotide variant
Location: chr2:95908690 (GRCh38)
Gene constraint: LOEUF 0.34 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 52.44
Residue 955: the 'disordered' region

Full ANKRD36C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD36C p.Asp1960His Conflicting classifications of pathogenicity ★ ⚠ same type
ANKRD36C p.Asp1068= Likely benign ★ same type
ANKRD36C p.Asp2046Asn Likely benign ★ same type
ANKRD36C p.Asp742= Likely benign ★ same type
ANKRD36C p.Asp966= Likely benign ★ same type
ANKRD36C p.Gln2014= Likely benign ★ same type
ANKRD36C p.His1888= Likely benign ★ same type
ANKRD36C p.Ile1666= 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/ankrd36c-p-ser955 (accessed [today's date]).

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