Is RLIM p.Ser6Phe (c.17C>T) pathogenic?

RLIM p.Ser6Phe (c.17C>T) is classified Likely benign in RLIM (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-30). AlphaMissense: likely benign (0.1756); Ultra-rare (popmax 0.0863%, sas); Associated with intellectual disability, X-linked 61.

What condition is associated with RLIM p.Ser6Phe (c.17C>T)?

RLIM p.Ser6Phe (c.17C>T) is associated with intellectual disability, X-linked 61 (ClinVar).

How common is RLIM p.Ser6Phe (c.17C>T) in the general population?

RLIM p.Ser6Phe (c.17C>T) is ultra-rare (popmax 0.0863%, sas) (gnomAD).

What do computational predictors say about RLIM p.Ser6Phe (c.17C>T)?

AlphaMissense predicts likely benign (score 0.1756) — an in-silico prediction, not a clinical call.

RLIM p.Ser6Phe

c.17C>T · VCV3892292

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1756 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0863%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability, X-linked 61

Computational evidence

Protein change
AlphaMissense	0.1756	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -9.73	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 4.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 2,957 bp · p 0.27 · regional, not allelic
Overall
CADD	22.4	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 0.0863% South Asian · 44/51,002 alleles

Filtering AF 0.066% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0589%

Overall 0.00398% 47/1,182,034 alleles · ultra-rare exomes 44/1,069,747 · genomes 3/112,287 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0863%	1,159
Middle Eastern	0.0236%	4,243
Remaining individualsnot grpmax-eligible	0.0043%	23,246

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.Ser6Phe
Coding: c.17C>T
MANE Select: NM_016120
Type: single nucleotide variant
Location: chrX:74595961 (GRCh38)
Structure: AlphaFold pLDDT 50.55 · 3 PDB
Residue 6: 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-ser6phe (accessed [today's date]).

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