Is ENG p.Leu107= (c.319C>T) pathogenic?

ENG p.Leu107= (c.319C>T) is classified Likely benign in ENG (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). Very rare (popmax 0.0011%, sas).

How common is ENG p.Leu107= (c.319C>T) in the general population?

ENG p.Leu107= (c.319C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

ENG p.Leu107=

c.319C>T · rs751531848 · VCV2659516

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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 0.94	GERP -3.2, phastCons 0.39
Overall
CADD	1.543	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,070 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,614,182 alleles · very rare exomes 5/1,461,866 · genomes 0/152,316 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,070
European (non-Finnish)	0.000339%	295,009

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: ENG
Protein: p.Leu107=
Coding: c.319C>T
MANE Select: NM_001114753
dbSNP: rs751531848
Type: single nucleotide variant
Location: chr9:127829728 (GRCh38)
Gene constraint: LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 3 PDB
Residue 107: a β-strand; a UniProt-annotated variant site (in hht1); the 'required for interaction with gdf2' region; the 'or2' region

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

Similar variants

ENG p.Leu107Arg Uncertain significance ★ ⚠ same residue
ENG p.Leu107_Leu109del Uncertain significance ★ same residue
ENG p.Arg529His Pathogenic ★★★ same type
ENG p.Asn423Ser Likely pathogenic ★★★ ⚠ same type
ENG p.Cys382Tyr Pathogenic ★★★ same type
ENG p.Cys549Gly Likely pathogenic ★★★ same type
ENG p.Gly331Ser Pathogenic ★★★ ⚠ same type
ENG p.Gly603Arg Likely pathogenic ★★★ same type

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/eng-p-leu107 (accessed [today's date]).

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