Is NRAP p.Ser84Ile (c.251G>T) pathogenic?

NRAP p.Ser84Ile (c.251G>T) is classified Likely benign in NRAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-09). AlphaMissense: likely benign (0.1302); Rare (popmax 0.27%, mid).

How common is NRAP p.Ser84Ile (c.251G>T) in the general population?

NRAP p.Ser84Ile (c.251G>T) is rare (popmax 0.27%, mid) (gnomAD).

What do computational predictors say about NRAP p.Ser84Ile (c.251G>T)?

AlphaMissense predicts likely benign (score 0.1302) — an in-silico prediction, not a clinical call.

NRAP p.Ser84Ile

c.251G>T · rs145242709 · VCV3895306

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1302 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.27%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1302	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -8.07	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 -0.096	GERP -2.7, phastCons 0.002
Overall
CADD	12.91	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 0.27% Middle Eastern · 16/5,924 alleles

Filtering AF 0.169% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.138%

Overall 0.0367% 562/1,532,054 alleles · rare exomes 530/1,379,778 · genomes 32/152,276 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.27%	370
Ashkenazi Jewishnot grpmax-eligible	0.24%	416
South Asian	0.151%	664
Remaining individualsnot grpmax-eligible	0.0519%	1,928
European (non-Finnish)	0.0268%	3,733
Admixed American	0.015%	6,646
African / African-American	0.00409%	24,451
East Asian	0.00225%	44,472
Finnishnot grpmax-eligible	0.00156%	63,946

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: NRAP
Protein: p.Ser84Ile
Coding: c.251G>T
MANE Select: NM_198060
dbSNP: rs145242709
Type: single nucleotide variant
Location: chr10:113662683 (GRCh38)
Gene constraint: LOEUF 1.045 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 51.98

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

Similar variants

NRAP p.Arg1037Ter Pathogenic/Likely pathogenic ★★ same type
NRAP p.Trp1033Ter Pathogenic/Likely pathogenic ★★ same type
NRAP c.360+1G>A Uncertain significance ★★ same type
NRAP p.Ala29Gly Uncertain significance ★★ ⚠ same type
NRAP p.Ala571Thr Uncertain significance ★★ same type
NRAP p.Arg1330Gln Uncertain significance ★★ ⚠ same type
NRAP p.Arg1559Gln Uncertain significance ★★ ⚠ same type
NRAP p.Arg428Cys 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/nrap-p-ser84ile (accessed [today's date]).

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