Is ANKRD1 p.Met1Val (c.1A>G) pathogenic?

ANKRD1 p.Met1Val (c.1A>G) is classified Uncertain significance in ANKRD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-29). Very rare (popmax 0.00223%, eas); Associated with ANKRD1-related dilated cardiomyopathy.

What condition is associated with ANKRD1 p.Met1Val (c.1A>G)?

ANKRD1 p.Met1Val (c.1A>G) is associated with ANKRD1-related dilated cardiomyopathy (ClinVar).

How common is ANKRD1 p.Met1Val (c.1A>G) in the general population?

ANKRD1 p.Met1Val (c.1A>G) is very rare (popmax 0.00223%, eas) (gnomAD).

ANKRD1 p.Met1Val

c.1A>G · rs772918277 · VCV1399465

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

start-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

ANKRD1-related dilated cardiomyopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function
REVEL	0.402	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP 2.2, phastCons 1
Overall
CADD	21.5	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,886 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.00143% 23/1,613,926 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
East Asiangrpmax	0.00223%	44,886
European (non-Finnish)	0.0017%	58,996
Finnishnot grpmax-eligible	0.00156%	64,016

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ANKRD1
Protein: p.Met1Val
Coding: c.1A>G
MANE Select: NM_014391
dbSNP: rs772918277
Type: single nucleotide variant
Location: chr10:90921027 (GRCh38)
Gene constraint: LOEUF 1.038 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.64

Full ANKRD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ANKRD1-related dilated cardiomyopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ANKRD1 p.Met1Ile Uncertain significance same residue
ANKRD1 c.651+6C>T Uncertain significance ★★ same condition
ANKRD1 c.652-2A>T Uncertain significance ★★ same condition
ANKRD1 c.849+1G>C Uncertain significance ★★ same condition
ANKRD1 p.Ala175Thr Uncertain significance ★★ ⚠ same condition
ANKRD1 p.Ala259Val Uncertain significance ★★ ⚠ same condition
ANKRD1 p.Arg100Ser Uncertain significance ★★ ⚠ same condition
ANKRD1 p.Arg154Trp Uncertain significance ★★ ⚠ 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/ankrd1-p-met1val (accessed [today's date]).

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