Is ANKRD49 p.Asn7Ser (c.20A>G) pathogenic?

ANKRD49 p.Asn7Ser (c.20A>G) is classified Uncertain significance in ANKRD49 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-29). AlphaMissense: likely benign (0.0788); Ultra-rare (popmax 0.0169%, mid).

How common is ANKRD49 p.Asn7Ser (c.20A>G) in the general population?

ANKRD49 p.Asn7Ser (c.20A>G) is ultra-rare (popmax 0.0169%, mid) (gnomAD).

What do computational predictors say about ANKRD49 p.Asn7Ser (c.20A>G)?

AlphaMissense predicts likely benign (score 0.0788) — an in-silico prediction, not a clinical call.

ANKRD49 p.Asn7Ser

c.20A>G · rs779671056 · VCV2298995

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0788 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0169%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0788	likely benign
REVEL	0.014	strongly benign-leaning
SaProt	LLR -5.68	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 1.3	GERP 0.45, phastCons 0.98
Regional constraint	o/e 0.77	unconstrained · MANE · 1,835 bp · p 0.00015 · regional, not allelic
Overall
CADD	11.98	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0169% Middle Eastern · 1/5,910 alleles

Filtering AF 0.00093% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000458%

Overall 0.00101% 16/1,582,372 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0177%	5,636
Middle Easterngrpmax	0.0169%	5,910
Remaining individualsnot grpmax-eligible	0.00819%	12,212
South Asian	0.0035%	28,551
European (non-Finnish)	0.000171%	583,880

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: ANKRD49
Protein: p.Asn7Ser
Coding: c.20A>G
MANE Select: NM_017704
dbSNP: rs779671056
Type: single nucleotide variant
Location: chr11:94496713 (GRCh38)
Gene constraint: LOEUF 1.221 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.73

Full ANKRD49 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKRD49 p.Asn85Lys Uncertain significance ★ ⚠ same type
ANKRD49 p.Gln162Lys Uncertain significance ★ ⚠ same type
ANKRD49 p.Glu54Lys Uncertain significance ★ ⚠ same type
ANKRD49 p.Glu83Asp Uncertain significance ★ ⚠ same type
ANKRD49 p.Lys58Glu Uncertain significance ★ ⚠ same type
ANKRD49 p.Lys97Asn Uncertain significance ★ ⚠ same type
ANKRD49 p.Met70Lys Uncertain significance ★ ⚠ same type
ANKRD49 p.Pro111Ser 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/ankrd49-p-asn7ser (accessed [today's date]).

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