Is RNPEP p.Ala258Val (c.773C>T) pathogenic?

RNPEP p.Ala258Val (c.773C>T) is classified Uncertain significance in RNPEP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-17). AlphaMissense: likely benign (0.1123); Very rare (popmax 0.00133%, afr).

How common is RNPEP p.Ala258Val (c.773C>T) in the general population?

RNPEP p.Ala258Val (c.773C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about RNPEP p.Ala258Val (c.773C>T)?

AlphaMissense predicts likely benign (score 0.1123) — an in-silico prediction, not a clinical call.

RNPEP p.Ala258Val

c.773C>T · rs1191114043 · VCV3155544

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1123 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1123	likely benign
REVEL	0.133	moderately benign-leaning
SaProt	LLR -9.19	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 -0.78	GERP -1.7
Regional constraint	o/e 0.92	unconstrained · MANE · 23 kb · p 0.025 · regional, not allelic
Overall
CADD	14.98	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 0.00133% African / African-American · 1/74,924 alleles

Overall 0.000657% 1/152,180 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: RNPEP
Protein: p.Ala258Val
Coding: c.773C>T
MANE Select: NM_020216
dbSNP: rs1191114043
Type: single nucleotide variant
Location: chr1:201996182 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.04

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

Similar variants

RNPEP p.Arg317Cys Benign ★★ ⚠ same type
RNPEP p.Thr184= Benign ★★ same type
RNPEP p.Ala339Thr Uncertain significance ★ same type
RNPEP p.Ala354Thr Uncertain significance ★ same type
RNPEP p.Ala365Thr Uncertain significance ★ ⚠ same type
RNPEP p.Arg176Trp Uncertain significance ★ ⚠ same type
RNPEP p.Arg376Gln Uncertain significance ★ ⚠ same type
RNPEP p.Arg380His 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/rnpep-p-ala258val (accessed [today's date]).

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