Is OBSL1 p.Ser367Phe (c.1100C>T) pathogenic?

OBSL1 p.Ser367Phe (c.1100C>T) is classified Uncertain significance in OBSL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-08). AlphaMissense: ambiguous (0.4162); Very rare (popmax 0.00439%, sas); Associated with Inborn genetic diseases.

What condition is associated with OBSL1 p.Ser367Phe (c.1100C>T)?

OBSL1 p.Ser367Phe (c.1100C>T) is associated with Inborn genetic diseases (ClinVar).

How common is OBSL1 p.Ser367Phe (c.1100C>T) in the general population?

OBSL1 p.Ser367Phe (c.1100C>T) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about OBSL1 p.Ser367Phe (c.1100C>T)?

AlphaMissense predicts ambiguous (score 0.4162) — an in-silico prediction, not a clinical call.

OBSL1 p.Ser367Phe

c.1100C>T · VCV4861382

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4162 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4162	ambiguous
REVEL	0.225	benign-leaning
SaProt	LLR -9.64	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP -0.81, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 3,541 bp · p 0.7 · regional, not allelic
Overall
CADD	25.4	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 0.00439% South Asian · 4/91,062 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.00031% 5/1,613,232 alleles · very rare exomes 4/1,460,998 · genomes 1/152,234 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,766
Remaining individualsnot grpmax-eligible	0.0016%	62,432

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.Ser367Phe
Coding: c.1100C>T
MANE Select: NM_015311
Type: single nucleotide variant
Location: chr2:219568237 (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 367: the ig-like 4 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

OBSL1 p.Ala1076Val Uncertain significance ★★ ⚠ same condition
OBSL1 p.Ala1143Thr Uncertain significance ★★ ⚠ same condition
OBSL1 p.Ala1175Pro Uncertain significance ★★ ⚠ same condition
OBSL1 p.Ala1186Val Uncertain significance ★★ ⚠ same condition
OBSL1 p.Ala1234Thr Uncertain significance ★★ ⚠ same condition
OBSL1 p.Ala1343Val Uncertain significance ★★ ⚠ same condition
OBSL1 p.Ala1613Val Uncertain significance ★★ ⚠ same condition
OBSL1 p.Ala167Val 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-ser367phe (accessed [today's date]).

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