Is RLIM p.Ser276Pro (c.826T>C) pathogenic?

RLIM p.Ser276Pro (c.826T>C) is classified Conflicting classifications of pathogenicity in RLIM (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-04-16). AlphaMissense: likely benign (0.0783); Ultra-rare (popmax 0.0385%, eas); Associated with intellectual disability, X-linked 61.

What condition is associated with RLIM p.Ser276Pro (c.826T>C)?

RLIM p.Ser276Pro (c.826T>C) is associated with intellectual disability, X-linked 61 (ClinVar).

How common is RLIM p.Ser276Pro (c.826T>C) in the general population?

RLIM p.Ser276Pro (c.826T>C) is ultra-rare (popmax 0.0385%, eas) (gnomAD).

What do computational predictors say about RLIM p.Ser276Pro (c.826T>C)?

AlphaMissense predicts likely benign (score 0.0783) — an in-silico prediction, not a clinical call.

RLIM p.Ser276Pro

c.826T>C · rs768846788 · VCV2435439

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0783 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0385%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability, X-linked 61

Computational evidence

Protein change
AlphaMissense	0.0783	likely benign
REVEL	0.156	moderately benign-leaning
SaProt	LLR -6.58	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.1	phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 685 bp · p 5.4e-06 · regional, not allelic
Overall
CADD	15.87	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

Grpmax group 0.0385% East Asian · 13/33,775 alleles

Filtering AF 0.0228% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.018%

Overall 0.00132% 16/1,210,048 alleles · ultra-rare exomes 15/1,098,124 · genomes 1/111,924 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0385%	2,598
Remaining individualsnot grpmax-eligible	0.0042%	23,799
South Asian	0.00176%	56,857

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.Ser276Pro
Coding: c.826T>C
MANE Select: NM_016120
dbSNP: rs768846788
Type: single nucleotide variant
Location: chrX:74592489 (GRCh38)
Structure: AlphaFold pLDDT 50.55 · 3 PDB
Residue 276: a modified residue (phosphoserine); the 'disordered' region

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

Disease context

intellectual disability, X-linked 61 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RLIM p.Arg365Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
RLIM p.Arg387Cys Pathogenic/Likely pathogenic ★★ same condition
RLIM p.Asp598Asn Pathogenic/Likely pathogenic ★★ same condition
RLIM p.Arg372Gln Uncertain significance ★★ ⚠ same condition
RLIM p.Arg510Gln Uncertain significance ★★ ⚠ same condition
RLIM p.Ile246Val Uncertain significance ★★ ⚠ same condition
RLIM p.Met437Ile Uncertain significance ★★ ⚠ same condition
RLIM p.Ser503Leu 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-ser276pro (accessed [today's date]).

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