Is OBSL1 p.Pro155Ser (c.463C>T) pathogenic?

OBSL1 p.Pro155Ser (c.463C>T) is classified Uncertain significance in OBSL1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-15). AlphaMissense: ambiguous (0.5031); Rare (popmax 0.358%, eas); Associated with 3M syndrome 2.

What condition is associated with OBSL1 p.Pro155Ser (c.463C>T)?

OBSL1 p.Pro155Ser (c.463C>T) is associated with 3M syndrome 2 (ClinVar).

How common is OBSL1 p.Pro155Ser (c.463C>T) in the general population?

OBSL1 p.Pro155Ser (c.463C>T) is rare (popmax 0.358%, eas) (gnomAD).

What do computational predictors say about OBSL1 p.Pro155Ser (c.463C>T)?

AlphaMissense predicts ambiguous (score 0.5031) — an in-silico prediction, not a clinical call.

OBSL1 p.Pro155Ser

c.463C>T · rs547450690 · VCV894883

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5031 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.358%, eas)

Conditions

3M syndrome 2

Computational evidence

Protein change
AlphaMissense	0.5031	ambiguous
REVEL	0.625	indeterminate
SaProt	LLR -12.78	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.1, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 3,541 bp · p 0.7 · regional, not allelic
Overall
CADD	26.3	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 0.358% East Asian · 123/34,354 alleles

Filtering AF 0.307% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.287%

Overall 0.00845% 126/1,491,186 alleles · rare exomes 117/1,339,252 · genomes 9/151,934 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.358%	279
Admixed American	0.0022%	45,510
Remaining individualsnot grpmax-eligible	0.00173%	57,954
European (non-Finnish)	8.87e-05%	1,127,427

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: OBSL1
Protein: p.Pro155Ser
Coding: c.463C>T
MANE Select: NM_015311
dbSNP: rs547450690
Type: single nucleotide variant
Location: chr2:219570770 (GRCh38)
Gene constraint: LOEUF 1.212 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 79.74 · 10 PDB
Residue 155: the ig-like 2 domain

Full OBSL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

3M syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

OBSL1 p.Gln678Ter Pathogenic ★★ same condition
OBSL1 c.4610-6G>A Uncertain significance ★★ same condition
OBSL1 c.-209C>G Uncertain significance ★★ same condition
OBSL1 c.-51A>C Uncertain significance ★★ same condition
OBSL1 p.Ala706Pro Uncertain significance ★★ ⚠ same condition
OBSL1 p.Ala90Thr Uncertain significance ★★ ⚠ same condition
OBSL1 p.Arg1043Cys Uncertain significance ★★ ⚠ same condition
OBSL1 p.Arg1098Cys 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/obsl1-p-pro155ser (accessed [today's date]).

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