Is ANKRD6 p.Ser121Arg (c.363C>A) pathogenic?

ANKRD6 p.Ser121Arg (c.363C>A) is classified Uncertain significance in ANKRD6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-15). AlphaMissense: likely pathogenic (0.9637); No allele count reported in gnomAD v4.1 (AN 1,595,166).

How common is ANKRD6 p.Ser121Arg (c.363C>A) in the general population?

ANKRD6 p.Ser121Arg (c.363C>A) is no allele count reported in gnomAD v4.1 (AN 1,595,166) (gnomAD).

What do computational predictors say about ANKRD6 p.Ser121Arg (c.363C>A)?

AlphaMissense predicts likely pathogenic (score 0.9637) — an in-silico prediction, not a clinical call.

ANKRD6 p.Ser121Arg

c.363C>A · VCV4833908

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9637 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,595,166)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9637	likely pathogenic · top 8% in ANKRD6
REVEL	0.391	indeterminate
SaProt	LLR -9.89	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 0.26, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 64 kb · p 0.065 · regional, not allelic
Overall
CADD	25.2	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

No allele count reported in gnomAD v4.1 (AN 1,595,166). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ANKRD6
Protein: p.Ser121Arg
Coding: c.363C>A
MANE Select: NM_001242809
Type: single nucleotide variant
Location: chr6:89606051 (GRCh38)
Gene constraint: LOEUF 0.869 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.82

Full ANKRD6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD6 p.Ala140Val Uncertain significance ★ ⚠ same type
ANKRD6 p.Ala173Glu Uncertain significance ★ same type
ANKRD6 p.Ala182Val Uncertain significance ★ ⚠ same type
ANKRD6 p.Ala206Gly Uncertain significance ★ ⚠ same type
ANKRD6 p.Ala206Thr Uncertain significance ★ ⚠ same type
ANKRD6 p.Ala229Thr Uncertain significance ★ ⚠ same type
ANKRD6 p.Ala262Val Uncertain significance ★ ⚠ same type
ANKRD6 p.Ala390Ser 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/ankrd6-p-ser121arg (accessed [today's date]).

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