Is ANKS1B p.Pro970Ser (c.2908C>T) pathogenic?

ANKS1B p.Pro970Ser (c.2908C>T) is classified Uncertain significance in ANKS1B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-09). AlphaMissense: likely pathogenic (0.6971); Very rare (popmax 0.00729%, nfe).

How common is ANKS1B p.Pro970Ser (c.2908C>T) in the general population?

ANKS1B p.Pro970Ser (c.2908C>T) is very rare (popmax 0.00729%, nfe) (gnomAD).

What do computational predictors say about ANKS1B p.Pro970Ser (c.2908C>T)?

AlphaMissense predicts likely pathogenic (score 0.6971) — an in-silico prediction, not a clinical call.

ANKS1B p.Pro970Ser

c.2908C>T · rs771639722 · VCV2225136

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6971 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00729%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6971	likely pathogenic
REVEL	0.217	benign-leaning
SaProt	LLR -5.24	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.52	unconstrained · MANE · 403 kb · p 8.2e-27 · regional, not allelic
Overall
CADD	28.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00729% European (non-Finnish) · 86/1,179,838 alleles

Filtering AF 0.00604% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00557%

Overall 0.00545% 88/1,613,792 alleles · very rare exomes 87/1,461,598 · genomes 1/152,194 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00729%	13,719
Remaining individualsnot grpmax-eligible	0.0032%	31,231

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: ANKS1B
Protein: p.Pro970Ser
Coding: c.2908C>T
MANE Select: NM_001352186
dbSNP: rs771639722
Type: single nucleotide variant
Location: chr12:98829332 (GRCh38)
Gene constraint: LOEUF 0.298 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 57.16 · 4 PDB
Residue 970: the 'disordered' region

Full ANKS1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKS1B p.Gly501Asp Uncertain significance ★★ ⚠ same type
ANKS1B c.1757-10C>T Benign ★★ same type
ANKS1B p.Arg157= Benign ★★ same type
ANKS1B p.Gly2= Benign ★★ same type
ANKS1B p.Leu681= Likely benign ★★ same type
ANKS1B p.Val288Met Benign ★★ same type
ANKS1B p.Val389Ala Benign ★★ same type
ANKS1B c.3441+2T>C Likely pathogenic ★ 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/anks1b-p-pro970ser (accessed [today's date]).

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