Is ANKRD2 p.Ser106Trp (c.317C>G) pathogenic?

ANKRD2 p.Ser106Trp (c.317C>G) is classified Uncertain significance in ANKRD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-22). AlphaMissense: likely benign (0.2744); Absent from gnomAD v4.1.

How common is ANKRD2 p.Ser106Trp (c.317C>G) in the general population?

ANKRD2 p.Ser106Trp (c.317C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANKRD2 p.Ser106Trp (c.317C>G)?

AlphaMissense predicts likely benign (score 0.2744) — an in-silico prediction, not a clinical call.

ANKRD2 p.Ser106Trp

c.317C>G · VCV4640725

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2744 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2744	likely benign
REVEL	0.165	moderately benign-leaning
SaProt	LLR -9.55	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP 1.8, phastCons 0.47
Regional constraint	o/e 0.92	unconstrained · MANE · 11 kb · p 0.092 · regional, not allelic
Overall
CADD	21.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S133W vs ClinVar S106W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ANKRD2
Protein: p.Ser106Trp
Coding: c.317C>G
MANE Select: NM_001346793
Type: single nucleotide variant
Location: chr10:97578367 (GRCh38)
Gene constraint: LOEUF 1.426 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.30
Residue 106: the 'may mediate interaction with pml, p53/tp53 and ybx1' region

Full ANKRD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD2 p.Ala285= Benign ★★ same type
ANKRD2 p.Pro119Leu Benign/Likely benign ★★ ⚠ same type
ANKRD2 p.Pro6Arg Benign ★★ same type
ANKRD2 p.Ala10Val Uncertain significance ★ ⚠ same type
ANKRD2 p.Ala128Val Uncertain significance ★ ⚠ same type
ANKRD2 p.Ala12Thr Uncertain significance ★ ⚠ same type
ANKRD2 p.Ala311Val Uncertain significance ★ ⚠ same type
ANKRD2 p.Arg100Pro 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/ankrd2-p-ser106trp (accessed [today's date]).

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