Is RALA p.Phe101Ser (c.302T>C) pathogenic?

RALA p.Phe101Ser (c.302T>C) is classified Uncertain significance in RALA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-11-10). AlphaMissense: likely pathogenic (0.9971); Absent from gnomAD v4.1; Associated with RALA-related disorder.

What condition is associated with RALA p.Phe101Ser (c.302T>C)?

RALA p.Phe101Ser (c.302T>C) is associated with RALA-related disorder (ClinVar).

How common is RALA p.Phe101Ser (c.302T>C) in the general population?

RALA p.Phe101Ser (c.302T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RALA p.Phe101Ser (c.302T>C)?

AlphaMissense predicts likely pathogenic (score 0.9971) — an in-silico prediction, not a clinical call.

RALA p.Phe101Ser

c.302T>C · rs1053085090 · VCV1507572

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9971 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

RALA-related disorder

Computational evidence

Protein change
AlphaMissense	0.9971	likely pathogenic
REVEL	0.969	strongly pathogenic-leaning
SaProt	LLR -14.70	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	28.6	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

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.Phe101Ser
Coding: c.302T>C
MANE Select: NM_005402
dbSNP: rs1053085090
Type: single nucleotide variant
Location: chr7:39690569 (GRCh38)
Gene constraint: LOEUF 0.54 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 89.54 · 17 PDB
Residue 101: an α-helix

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

Disease context

RALA-related disorder

Similar variants

RALA p.Cys204Tyr Uncertain significance ★ ⚠ same condition
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 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-phe101ser (accessed [today's date]).

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