Is ERF p.Leu384= (c.1152C>T) pathogenic?

ERF p.Leu384= (c.1152C>T) is classified Likely benign in ERF (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-24). Very rare (popmax 0.00549%, sas); Associated with TWIST1-related craniosynostosis.

What condition is associated with ERF p.Leu384= (c.1152C>T)?

ERF p.Leu384= (c.1152C>T) is associated with TWIST1-related craniosynostosis (ClinVar).

How common is ERF p.Leu384= (c.1152C>T) in the general population?

ERF p.Leu384= (c.1152C>T) is very rare (popmax 0.00549%, sas) (gnomAD).

ERF p.Leu384=

c.1152C>T · rs772786203 · VCV1592634

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Conditions

TWIST1-related craniosynostosis

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 -3.7	GERP -2.8
Overall
CADD	1.874	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,062 alleles

Filtering AF 0.00299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00267%

Overall 0.00367% 59/1,606,530 alleles · very rare exomes 54/1,454,326 · genomes 5/152,204 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,212
African / African-American	0.004%	24,976
European (non-Finnish)	0.0039%	25,643
Admixed American	0.00333%	29,990
East Asian	0.00223%	44,868
Finnishnot grpmax-eligible	0.00175%	57,130
Remaining individualsnot grpmax-eligible	0.0016%	62,394

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: ERF
Protein: p.Leu384=
Coding: c.1152C>T
MANE Select: NM_006494
dbSNP: rs772786203
Type: single nucleotide variant
Location: chr19:42248960 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 55.46 · 2 PDB
Residue 384: the 'disordered' region

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

Disease context

TWIST1-related craniosynostosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ERF p.Arg183Ter Pathogenic ★★ same condition
ERF p.Arg207Ter Pathogenic/Likely pathogenic ★★ same condition
ERF p.Arg218Ter Pathogenic/Likely pathogenic ★★ same condition
ERF p.Arg86Cys Pathogenic/Likely pathogenic ★★ same condition
ERF p.Ser24Ter Pathogenic/Likely pathogenic ★★ same condition
ERF p.Arg458Gly Uncertain significance ★★ ⚠ same condition
ERF p.Arg493His Uncertain significance ★★ ⚠ same condition
ERF p.Lys401Glu 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/erf-p-leu384 (accessed [today's date]).

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