Is ANKRD6 p.Ser152Arg (c.454A>C) pathogenic?

ANKRD6 p.Ser152Arg (c.454A>C) is classified Uncertain significance in ANKRD6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-13). AlphaMissense: likely pathogenic (0.8199); Very rare (popmax 0.000433%, nfe).

How common is ANKRD6 p.Ser152Arg (c.454A>C) in the general population?

ANKRD6 p.Ser152Arg (c.454A>C) is very rare (popmax 0.000433%, nfe) (gnomAD).

What do computational predictors say about ANKRD6 p.Ser152Arg (c.454A>C)?

AlphaMissense predicts likely pathogenic (score 0.8199) — an in-silico prediction, not a clinical call.

ANKRD6 p.Ser152Arg

c.454A>C · rs1286741568 · VCV2284091

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8199 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000433%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8199	likely pathogenic
REVEL	0.246	benign-leaning
SaProt	LLR -6.91	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 7.9	GERP 0.29, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 64 kb · p 0.065 · regional, not allelic
Overall
CADD	24.2	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

Grpmax group 0.000433% European (non-Finnish) · 5/1,154,386 alleles

Filtering AF 0.000127% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.2e-05%

Overall 0.000319% 5/1,565,358 alleles · very rare exomes 5/1,413,018 · genomes 0/152,340 · joint denominator

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: ANKRD6
Protein: p.Ser152Arg
Coding: c.454A>C
MANE Select: NM_001242809
dbSNP: rs1286741568
Type: single nucleotide variant
Location: chr6:89612308 (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-ser152arg (accessed [today's date]).

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