Is NES p.Lys830Arg (c.2489A>G) pathogenic?

NES p.Lys830Arg (c.2489A>G) is classified Benign in NES (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.0901); Low-frequency (popmax 4.48%, afr).

How common is NES p.Lys830Arg (c.2489A>G) in the general population?

NES p.Lys830Arg (c.2489A>G) is low-frequency (popmax 4.48%, afr) (gnomAD).

What do computational predictors say about NES p.Lys830Arg (c.2489A>G)?

AlphaMissense predicts likely benign (score 0.0901) — an in-silico prediction, not a clinical call.

NES p.Lys830Arg

c.2489A>G · rs114315457 · VCV791612

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0901 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.48%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0901	likely benign
REVEL	0.154	moderately benign-leaning
SaProt	LLR -6.40	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 -0.84	GERP -3.7
Regional constraint	o/e 0.94	unconstrained · MANE · 7,939 bp · p 0.0089 · regional, not allelic
Overall
CADD	7.182	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 4.48% African / African-American · 3,357/74,998 alleles

Filtering AF 4.35% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.3%

Overall 0.229% 3,701/1,613,908 alleles · low-frequency exomes 1,840/1,461,552 · genomes 1,861/152,356 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.48%	22
Remaining individualsnot grpmax-eligible	0.258%	388
Middle Eastern	0.231%	433
Admixed American	0.208%	480
South Asian	0.00659%	15,177
European (non-Finnish)	0.00322%	31,052

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: NES
Protein: p.Lys830Arg
Coding: c.2489A>G
MANE Select: NM_006617
dbSNP: rs114315457
Type: single nucleotide variant
Location: chr1:156671699 (GRCh38)
Gene constraint: LOEUF 1.264 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 49.18
Residue 830: the 'tail' region

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

Similar variants

NES p.Glu8Val Uncertain significance ★★ ⚠ same type
NES p.Arg342Gln Benign ★★ same type
NES p.Glu609Gln Benign ★★ same type
NES p.Gly1407Arg Benign ★★ same type
NES p.Leu412= Benign ★★ same type
NES p.Pro1275Leu Benign ★★ same type
NES p.Ser1466Gly Benign ★★ same type
NES p.Ala1050Thr 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/nes-p-lys830arg (accessed [today's date]).

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