Is OBSL1 p.Pro243= (c.729G>A) pathogenic?

OBSL1 p.Pro243= (c.729G>A) is classified Benign/Likely benign in OBSL1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-02). Rare (popmax 0.858%, eas); Associated with 3M syndrome 2.

What condition is associated with OBSL1 p.Pro243= (c.729G>A)?

OBSL1 p.Pro243= (c.729G>A) is associated with 3M syndrome 2 (ClinVar).

How common is OBSL1 p.Pro243= (c.729G>A) in the general population?

OBSL1 p.Pro243= (c.729G>A) is rare (popmax 0.858%, eas) (gnomAD).

OBSL1 p.Pro243=

c.729G>A · rs200417841 · VCV334532

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.858%, eas)

Conditions

3M syndrome 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5	GERP -2.2
Overall
CADD	5.351	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.858% East Asian · 384/44,732 alleles

Filtering AF 0.788% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.76%

Overall 0.0256% 413/1,611,368 alleles · rare exomes 362/1,459,366 · genomes 51/152,002 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.858%	116
Remaining individualsnot grpmax-eligible	0.0289%	3,466
South Asian	0.00879%	11,372
Admixed American	0.00167%	59,946
European (non-Finnish)	0.00017%	589,553

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.Pro243=
Coding: c.729G>A
MANE Select: NM_015311
dbSNP: rs200417841
Type: single nucleotide variant
Location: chr2:219570504 (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 243: the ig-like 3 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.Pro243Ala Uncertain significance ★★ ⚠ same residue
OBSL1 p.Pro243Gln Uncertain significance ★★ ⚠ same residue
OBSL1 p.Pro243Arg Uncertain significance ★ ⚠ same residue
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

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-pro243 (accessed [today's date]).

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