Is RLIM p.Ser309Pro (c.925T>C) pathogenic?

RLIM p.Ser309Pro (c.925T>C) is classified Uncertain significance in RLIM (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-06). AlphaMissense: likely benign (0.0791); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with RLIM p.Ser309Pro (c.925T>C)?

RLIM p.Ser309Pro (c.925T>C) is associated with Inborn genetic diseases (ClinVar).

How common is RLIM p.Ser309Pro (c.925T>C) in the general population?

RLIM p.Ser309Pro (c.925T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RLIM p.Ser309Pro (c.925T>C)?

AlphaMissense predicts likely benign (score 0.0791) — an in-silico prediction, not a clinical call.

RLIM p.Ser309Pro

c.925T>C · rs2519834574 · VCV2557647

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0791 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0791	likely benign
REVEL	0.084	moderately benign-leaning
SaProt	LLR -7.50	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 2.5	phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 685 bp · p 5.4e-06 · regional, not allelic
Overall
CADD	15.56	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: RLIM
Protein: p.Ser309Pro
Coding: c.925T>C
MANE Select: NM_016120
dbSNP: rs2519834574
Type: single nucleotide variant
Location: chrX:74592390 (GRCh38)
Structure: AlphaFold pLDDT 50.55 · 3 PDB
Residue 309: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RLIM p.Arg387Cys Pathogenic/Likely pathogenic ★★ same condition
RLIM p.Arg162His Uncertain significance ★★ ⚠ same condition
RLIM p.Ile98Val Uncertain significance ★★ ⚠ same condition
RLIM p.Gly448Asp Likely benign ★★ same condition
RLIM p.Ile98Leu Likely benign ★★ same condition
RLIM p.Ser471= Likely benign ★★ same condition
RLIM p.Arg180Leu Uncertain significance ★ ⚠ same condition
RLIM p.Arg443Gln Uncertain significance ★ ⚠ 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/rlim-p-ser309pro (accessed [today's date]).

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