Is ANKAR p.Asn1418Ser (c.4253A>G) pathogenic?

ANKAR p.Asn1418Ser (c.4253A>G) is classified Likely benign in ANKAR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-10). AlphaMissense: likely benign (0.0584); Very rare (popmax 6.84e-05%).

How common is ANKAR p.Asn1418Ser (c.4253A>G) in the general population?

ANKAR p.Asn1418Ser (c.4253A>G) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about ANKAR p.Asn1418Ser (c.4253A>G)?

AlphaMissense predicts likely benign (score 0.0584) — an in-silico prediction, not a clinical call.

ANKAR p.Asn1418Ser

c.4253A>G · rs2044197350 · VCV2325823

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0584 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0584	likely benign
REVEL	0.09	moderately benign-leaning
SaProt	LLR -5.49	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 -0.2	GERP -2.9
Regional constraint	o/e 0.93	unconstrained · MANE · 70 kb · p 0.0059 · regional, not allelic
Overall
CADD	0.327	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 6.84e-05%

Overall 6.84e-05% 1/1,460,972 alleles · very rare

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: ANKAR
Protein: p.Asn1418Ser
Coding: c.4253A>G
MANE Select: NM_001378068
dbSNP: rs2044197350
Type: single nucleotide variant
Location: chr2:189746575 (GRCh38)
Gene constraint: LOEUF 1.07 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.79

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

Similar variants

ANKAR p.Asn938= Benign ★★ same type
ANKAR p.Gln1419Leu Benign ★★ same type
ANKAR p.Ile1349= Benign ★★ same type
ANKAR p.Leu94Arg Benign ★★ same type
ANKAR p.Thr206Ala Benign ★★ same type
ANKAR p.Thr92= Benign ★★ same type
ANKAR p.Tyr1262Ser Benign ★★ same type
ANKAR p.Val776Ala Likely benign ★★ ⚠ 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/ankar-p-asn1418ser (accessed [today's date]).

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