Is ANKRD6 p.Ala347= (c.1041A>G) pathogenic?

ANKRD6 p.Ala347= (c.1041A>G) is classified Benign in ANKRD6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-17). Common (popmax 99.8%, eas) — too common for a highly-penetrant pathogenic allele; Associated with ANKRD6-related disorder.

What condition is associated with ANKRD6 p.Ala347= (c.1041A>G)?

ANKRD6 p.Ala347= (c.1041A>G) is associated with ANKRD6-related disorder (ClinVar).

ANKRD6 p.Ala347=

Q: How common is ANKRD6 p.Ala347= (c.1041A>G) in the general population?

ANKRD6 p.Ala347= (c.1041A>G) is common (popmax 99.8%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1041A>G · rs17292811 · VCV3060790

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 99.8%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

ANKRD6-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -3.2	GERP -3.5
Overall
CADD	1.497	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 99.8% East Asian · 44,794/44,868 alleles

Filtering AF 99.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 98.7%

Overall 84.7% 1,365,585/1,612,574 alleles · common exomes 1,234,735/1,460,504 · genomes 130,850/152,070 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	99.8%	1
Admixed American	92.1%	1
South Asian	87%	1
African / African-American	86.9%	1
Finnishnot grpmax-eligible	85.7%	1
Remaining individualsnot grpmax-eligible	85%	1
Amishnot grpmax-eligible	84.5%	1
European (non-Finnish)	83.5%	1
Ashkenazi Jewishnot grpmax-eligible	80.2%	1
Middle Eastern	76.6%	1

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.Ala347=
Coding: c.1041A>G
MANE Select: NM_001242809
dbSNP: rs17292811
Type: single nucleotide variant
Location: chr6:89623880 (GRCh38)
Gene constraint: LOEUF 0.869 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.82
Residue 347: the 'disordered' region

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

Disease context

ANKRD6-related disorder

Similar variants

ANKRD6 p.Ala550Thr Benign same condition
ANKRD6 p.Cys506= Benign same condition
ANKRD6 p.Gln122Glu Benign same condition
ANKRD6 p.Ile128Val Benign same condition
ANKRD6 p.Leu127= Likely benign same condition
ANKRD6 p.Pro636Leu Benign same condition
ANKRD6 p.Ser579= Benign same condition
ANKRD6 p.Thr157= Likely benign same condition

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-ala347 (accessed [today's date]).

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