Is AMER2 p.Asn617Ser (c.1850A>G) pathogenic?

AMER2 p.Asn617Ser (c.1850A>G) is classified Uncertain significance in AMER2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-04). AlphaMissense: likely benign (0.0651); Very rare (popmax 0.00933%, afr).

How common is AMER2 p.Asn617Ser (c.1850A>G) in the general population?

AMER2 p.Asn617Ser (c.1850A>G) is very rare (popmax 0.00933%, afr) (gnomAD).

What do computational predictors say about AMER2 p.Asn617Ser (c.1850A>G)?

AlphaMissense predicts likely benign (score 0.0651) — an in-silico prediction, not a clinical call.

AMER2 p.Asn617Ser

c.1850A>G · rs200341589 · VCV2599541

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0651 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00933%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0651	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -4.79	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 3.3	GERP 1.7, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 2,012 bp · p 0.5 · regional, not allelic
Overall
CADD	17.12	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 0.00933% African / African-American · 7/75,002 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00362%

Overall 0.00434% 70/1,614,050 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00933%	10,715
European (non-Finnish)	0.00508%	19,666
Remaining individualsnot grpmax-eligible	0.0032%	31,255
Admixed American	0.00167%	60,016

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: AMER2
Protein: p.Asn617Ser
Coding: c.1850A>G
MANE Select: NM_152704
dbSNP: rs200341589
Type: single nucleotide variant
Location: chr13:25169770 (GRCh38)
Gene constraint: LOEUF 0.655 · pLI 0.84 (gnomAD)
Structure: AlphaFold pLDDT 51.91

Full AMER2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AMER2 p.Ala158Gly Uncertain significance ★ ⚠ same type
AMER2 p.Ala158Pro Uncertain significance ★ ⚠ same type
AMER2 p.Ala212Val Uncertain significance ★ ⚠ same type
AMER2 p.Ala214Pro Uncertain significance ★ ⚠ same type
AMER2 p.Ala219Val Uncertain significance ★ ⚠ same type
AMER2 p.Ala245Ser Uncertain significance ★ ⚠ same type
AMER2 p.Ala260Glu Uncertain significance ★ ⚠ same type
AMER2 p.Ala319Pro 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/amer2-p-asn617ser (accessed [today's date]).

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