Is RLIM p.Ser463= (c.1389C>A) pathogenic?

RLIM p.Ser463= (c.1389C>A) is classified Likely benign in RLIM (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-28). Ultra-rare (popmax 0.0332%, nfe).

How common is RLIM p.Ser463= (c.1389C>A) in the general population?

RLIM p.Ser463= (c.1389C>A) is ultra-rare (popmax 0.0332%, nfe) (gnomAD).

RLIM p.Ser463=

c.1389C>A · rs773922290 · VCV1078562

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0332%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -8.9
Overall
CADD	0.06	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0332% European (non-Finnish) · 291/876,305 alleles

Filtering AF 0.03% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0288%

Overall 0.0304% 358/1,179,341 alleles · ultra-rare exomes 341/1,074,402 · genomes 17/104,939 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0627%	1,594
European (non-Finnish)grpmax	0.0332%	3,011
African / African-American	0.0255%	3,923
Remaining individualsnot grpmax-eligible	0.0236%	4,234
Middle Eastern	0.0234%	4,269
East Asian	0.0182%	5,505
Admixed American	0.0134%	7,448
Ashkenazi Jewishnot grpmax-eligible	0.00461%	21,678
South Asian	0.00184%	54,201

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: RLIM
Protein: p.Ser463=
Coding: c.1389C>A
MANE Select: NM_016120
dbSNP: rs773922290
Type: single nucleotide variant
Location: chrX:74591926 (GRCh38)
Structure: AlphaFold pLDDT 50.55 · 3 PDB
Residue 463: the 'disordered' region

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

Similar variants

RLIM p.Arg365Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
RLIM p.Arg387Cys Pathogenic/Likely pathogenic ★★ same type
RLIM p.Asp598Asn Pathogenic/Likely pathogenic ★★ same type
RLIM p.Arg162His Uncertain significance ★★ ⚠ same type
RLIM p.Arg372Gln Uncertain significance ★★ ⚠ same type
RLIM p.Arg510Gln Uncertain significance ★★ ⚠ same type
RLIM p.Asp337Glu Uncertain significance ★★ ⚠ same type
RLIM p.Ile246Val 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/rlim-p-ser463 (accessed [today's date]).

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