Is OBSL1 p.Phe255= (c.765C>T) pathogenic?

OBSL1 p.Phe255= (c.765C>T) is classified Conflicting classifications of pathogenicity in OBSL1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-20). Rare (popmax 0.127%, eas); Associated with 3M syndrome 2.

What condition is associated with OBSL1 p.Phe255= (c.765C>T)?

OBSL1 p.Phe255= (c.765C>T) is associated with 3M syndrome 2 (ClinVar).

How common is OBSL1 p.Phe255= (c.765C>T) in the general population?

OBSL1 p.Phe255= (c.765C>T) is rare (popmax 0.127%, eas) (gnomAD).

OBSL1 p.Phe255=

c.765C>T · rs751927713 · VCV899015

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.127%, 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 5.9	GERP 1.4, phastCons 1
Overall
CADD	14.53	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.127% East Asian · 57/44,832 alleles

Filtering AF 0.107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0994%

Overall 0.0117% 188/1,612,956 alleles · rare exomes 179/1,460,738 · genomes 9/152,218 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.127%	787
South Asian	0.125%	799
Remaining individualsnot grpmax-eligible	0.0256%	3,902
European (non-Finnish)	8.48e-05%	1,179,514

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.Phe255=
Coding: c.765C>T
MANE Select: NM_015311
dbSNP: rs751927713
Type: single nucleotide variant
Location: chr2:219570468 (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 255: the ig-like 3 domain; a β-strand

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-phe255 (accessed [today's date]).

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