Is RALA p.Ile205Val (c.613A>G) pathogenic?

RALA p.Ile205Val (c.613A>G) is classified Uncertain significance in RALA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-20). AlphaMissense: likely benign (0.1705); Absent from gnomAD v4.1.

How common is RALA p.Ile205Val (c.613A>G) in the general population?

RALA p.Ile205Val (c.613A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RALA p.Ile205Val (c.613A>G)?

AlphaMissense predicts likely benign (score 0.1705) — an in-silico prediction, not a clinical call.

RALA p.Ile205Val

c.613A>G · VCV4810432

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1705 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1705	likely benign
REVEL	0.204	benign-leaning
SaProt	LLR -6.74	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 6.2	GERP 2.2, phastCons 1
Regional constraint	o/e 0.39	unconstrained · MANE · 20 kb · p 4.8e-21 · regional, not allelic
Overall
CADD	21.2	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

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.Ile205Val
Coding: c.613A>G
MANE Select: NM_005402
Type: single nucleotide variant
Location: chr7:39706237 (GRCh38)
Gene constraint: LOEUF 0.54 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 89.54 · 17 PDB
Residue 205: a UniProt-annotated variant site (in hincons; uncertain significance)

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-ile205val (accessed [today's date]).

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