Is RALA p.Ser157Ala (c.469T>G) pathogenic?

RALA p.Ser157Ala (c.469T>G) is classified Pathogenic in RALA (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-05-06). AlphaMissense: likely pathogenic (0.8699); Absent from gnomAD v4.1; Associated with Hiatt-Neu-Cooper neurodevelopmental syndrome.

What condition is associated with RALA p.Ser157Ala (c.469T>G)?

RALA p.Ser157Ala (c.469T>G) is associated with Hiatt-Neu-Cooper neurodevelopmental syndrome (ClinVar).

How common is RALA p.Ser157Ala (c.469T>G) in the general population?

RALA p.Ser157Ala (c.469T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RALA p.Ser157Ala (c.469T>G)?

AlphaMissense predicts likely pathogenic (score 0.8699) — an in-silico prediction, not a clinical call.

RALA p.Ser157Ala

c.469T>G · rs2116098885 · VCV1068754

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8699 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Hiatt-Neu-Cooper neurodevelopmental syndrome

Computational evidence

Protein change
AlphaMissense	0.8699	likely pathogenic ✓ concordant with ClinVar
REVEL	0.923	moderately pathogenic-leaning
SaProt	LLR -11.05	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 7.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.39	unconstrained · MANE · 20 kb · p 4.8e-21 · regional, not allelic
Overall
CADD	26.4	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.Ser157Ala
Coding: c.469T>G
MANE Select: NM_005402
dbSNP: rs2116098885
Type: single nucleotide variant
Location: chr7:39696830 (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

Hiatt-Neu-Cooper neurodevelopmental syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RALA p.Ser157Phe Pathogenic ★ same residue
RALA p.Ser157= Likely benign ★ same residue
RALA p.Thr156Ile Likely pathogenic ★★ same condition
RALA p.Val25Met Pathogenic/Likely pathogenic ★★ same condition
RALA p.Ala158Thr Likely pathogenic ★ same condition
RALA p.Asp130Glu Likely pathogenic ★ same condition
RALA p.Gly23Ala Likely pathogenic ★ same condition
RALA p.Lys16Glu Likely pathogenic ★ 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/rala-p-ser157ala (accessed [today's date]).

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