Is RALA p.Ser157Phe (c.470C>T) pathogenic?

RALA p.Ser157Phe (c.470C>T) is classified Pathogenic in RALA (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely pathogenic (0.9996); Absent from gnomAD v4.1; Associated with Neurodevelopmental delay.

What condition is associated with RALA p.Ser157Phe (c.470C>T)?

RALA p.Ser157Phe (c.470C>T) is associated with Neurodevelopmental delay (ClinVar).

How common is RALA p.Ser157Phe (c.470C>T) in the general population?

RALA p.Ser157Phe (c.470C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RALA p.Ser157Phe (c.470C>T)?

AlphaMissense predicts likely pathogenic (score 0.9996) — an in-silico prediction, not a clinical call.

RALA p.Ser157Phe

c.470C>T · rs2116098893 · VCV1700118

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9996 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Neurodevelopmental delay

Computational evidence

Protein change
AlphaMissense	0.9996	likely pathogenic ✓ concordant with ClinVar · top 3% in RALA
REVEL	0.945	strongly pathogenic-leaning
SaProt	LLR -16.05	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.39	unconstrained · MANE · 20 kb · p 4.8e-21 · regional, not allelic
Overall
CADD	31.0	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.Ser157Phe
Coding: c.470C>T
MANE Select: NM_005402
dbSNP: rs2116098893
Type: single nucleotide variant
Location: chr7:39696831 (GRCh38)
Gene constraint: LOEUF 0.54 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 89.54 · 17 PDB
Residue 157: a UniProt-annotated variant site (in hincons; decreased gtpase activity; increased rala effector binding)

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

Disease context

Neurodevelopmental delay — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RALA p.Ser157= Likely benign ★ same residue
RALA p.Ser157Ala Pathogenic same residue
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

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-ser157phe (accessed [today's date]).

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