Is RALA p.Val154Met (c.460G>A) pathogenic?

RALA p.Val154Met (c.460G>A) is classified Benign in RALA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-16). AlphaMissense: ambiguous (0.5314); Absent from gnomAD v4.1.

How common is RALA p.Val154Met (c.460G>A) in the general population?

RALA p.Val154Met (c.460G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RALA p.Val154Met (c.460G>A)?

AlphaMissense predicts ambiguous (score 0.5314) — an in-silico prediction, not a clinical call.

RALA p.Val154Met

c.460G>A · rs1182241643 · VCV2099688

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5314 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.5314	ambiguous
REVEL	0.529	indeterminate
SaProt	LLR -7.66	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.39	unconstrained · MANE · 20 kb · p 4.8e-21 · regional, not allelic
Overall
CADD	27.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RALA
Protein: p.Val154Met
Coding: c.460G>A
MANE Select: NM_005402
dbSNP: rs1182241643
Type: single nucleotide variant
Location: chr7:39696821 (GRCh38)
Gene constraint: LOEUF 0.54 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 89.54 · 17 PDB
Residue 154: a β-strand

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

Similar variants

RALA p.Thr156Ile Likely pathogenic ★★ same type
RALA p.Val25Met Pathogenic/Likely pathogenic ★★ same type
RALA p.Ala196Thr Uncertain significance ★★ ⚠ same type
RALA p.Arg161Ter Uncertain significance ★★ same type
RALA p.Arg176Ter Uncertain significance ★★ same type
RALA p.Asp37Asn Uncertain significance ★★ ⚠ same type
RALA p.Phe101Ser Uncertain significance ★★ ⚠ same type
RALA c.114+10A>T Benign/Likely benign ★★ 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/rala-p-val154met (accessed [today's date]).

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