Is ESCO2 p.Pro150= (c.450A>G) pathogenic?

ESCO2 p.Pro150= (c.450A>G) is classified Uncertain significance in ESCO2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-04-15). Very rare (popmax 0.00133%, afr); Associated with Roberts-SC phocomelia syndrome.

What condition is associated with ESCO2 p.Pro150= (c.450A>G)?

ESCO2 p.Pro150= (c.450A>G) is associated with Roberts-SC phocomelia syndrome (ClinVar).

How common is ESCO2 p.Pro150= (c.450A>G) in the general population?

ESCO2 p.Pro150= (c.450A>G) is very rare (popmax 0.00133%, afr) (gnomAD).

ESCO2 p.Pro150=

c.450A>G · VCV4067388

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

Roberts-SC phocomelia syndrome

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 0.48	GERP 0.61
Overall
CADD	3.509	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,066 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000434% 7/1,614,002 alleles · very rare exomes 7/1,461,640 · genomes 0/152,362 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,066
European (non-Finnish)	0.000508%	196,673

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: ESCO2
Protein: p.Pro150=
Coding: c.450A>G
MANE Select: NM_001017420
Type: single nucleotide variant
Location: chr8:27776758 (GRCh38)
Gene constraint: LOEUF 1.013 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 58.81

Full ESCO2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Roberts-SC phocomelia syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ESCO2 c.1013+1G>A Likely pathogenic ★★ same condition
ESCO2 c.1131+1G>A Pathogenic ★★ same condition
ESCO2 c.1131+1G>T Pathogenic ★★ same condition
ESCO2 c.1132-7A>G Pathogenic/Likely pathogenic ★★ same condition
ESCO2 c.1353+1G>T Likely pathogenic ★★ same condition
ESCO2 p.Arg169Ter Pathogenic ★★ same condition
ESCO2 p.Arg552Ter Pathogenic/Likely pathogenic ★★ same condition
ESCO2 p.Gln409Ter Pathogenic/Likely pathogenic ★★ 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/esco2-p-pro150 (accessed [today's date]).

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