Is LENG8 p.Arg616= (c.1848C>T) pathogenic?

LENG8 p.Arg616= (c.1848C>T) is classified Likely benign in LENG8 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-03). Ultra-rare (popmax 0.0165%, mid); Associated with LENG8-related disorder.

What condition is associated with LENG8 p.Arg616= (c.1848C>T)?

LENG8 p.Arg616= (c.1848C>T) is associated with LENG8-related disorder (ClinVar).

How common is LENG8 p.Arg616= (c.1848C>T) in the general population?

LENG8 p.Arg616= (c.1848C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

LENG8 p.Arg616=

c.1848C>T · rs551413817 · VCV3037344

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

LENG8-related disorder

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 -0.66	GERP 0.65, phastCons 0.008
Overall
CADD	2.34	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00143% 23/1,613,932 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
Admixed American	0.00333%	30,019
Remaining individualsnot grpmax-eligible	0.0032%	31,254
South Asian	0.0022%	45,541
European (non-Finnish)	0.00136%	73,753

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: LENG8
Protein: p.Arg616=
Coding: c.1848C>T
MANE Select: NM_052925
dbSNP: rs551413817
Type: single nucleotide variant
Location: chr19:54457948 (GRCh38)
Gene constraint: LOEUF 0.375 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.38 · 6 PDB

Full LENG8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

LENG8-related disorder

Similar variants

LENG8 c.1732-9C>T Benign same condition
LENG8 p.Ala597= Likely benign same condition
LENG8 p.Arg430Cys Benign same condition
LENG8 p.Gln85His Benign same condition
LENG8 p.Gly464= Likely benign same condition
LENG8 p.His34= Likely benign same condition
LENG8 p.Ile557Val Benign same condition
LENG8 p.Ile630= Benign 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/leng8-p-arg616 (accessed [today's date]).

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