Is NRAP p.Val693Asp (c.2078T>A) pathogenic?

NRAP p.Val693Asp (c.2078T>A) is classified Uncertain significance in NRAP (ClinVar, Single submitter, 2 submitters; last evaluated 2026-03-27). AlphaMissense: likely pathogenic (0.8133); Very rare (popmax 0.00534%, afr); Associated with Cardiovascular phenotype.

What condition is associated with NRAP p.Val693Asp (c.2078T>A)?

NRAP p.Val693Asp (c.2078T>A) is associated with Cardiovascular phenotype (ClinVar).

How common is NRAP p.Val693Asp (c.2078T>A) in the general population?

NRAP p.Val693Asp (c.2078T>A) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about NRAP p.Val693Asp (c.2078T>A)?

AlphaMissense predicts likely pathogenic (score 0.8133) — an in-silico prediction, not a clinical call.

NRAP p.Val693Asp

c.2078T>A · rs374679989 · VCV3356138

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8133 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.8133	likely pathogenic · top 7% in NRAP
REVEL	0.396	indeterminate
SaProt	LLR -13.39	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 2.1, phastCons 1
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00534% African / African-American · 4/74,960 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000434% 7/1,613,718 alleles · very rare exomes 7/1,461,602 · genomes 0/152,116 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,740
Remaining individualsnot grpmax-eligible	0.0032%	31,251
European (non-Finnish)	8.48e-05%	1,179,842

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.Val693Asp
Coding: c.2078T>A
MANE Select: NM_198060
dbSNP: rs374679989
Type: single nucleotide variant
Location: chr10:113628984 (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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NRAP p.Ala29Gly Uncertain significance ★★ ⚠ same condition
NRAP p.Arg1330Gln Uncertain significance ★★ ⚠ same condition
NRAP p.Arg428Cys Uncertain significance ★★ ⚠ same condition
NRAP p.Asn1233Lys Uncertain significance ★★ ⚠ same condition
NRAP p.Gly748Arg Uncertain significance ★★ ⚠ same condition
NRAP p.Pro769Leu Uncertain significance ★★ ⚠ same condition
NRAP p.Ser169Arg Uncertain significance ★★ ⚠ same condition
NRAP p.Thr903Met Uncertain significance ★★ ⚠ same condition

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-val693asp (accessed [today's date]).

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