Is ADAMTSL4 p.Pro620= (c.1860G>A) pathogenic?

ADAMTSL4 p.Pro620= (c.1860G>A) is classified Uncertain significance in ADAMTSL4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-04-11). Very rare (popmax 0.00803%, afr); Associated with ectopia lentis et pupillae.

What condition is associated with ADAMTSL4 p.Pro620= (c.1860G>A)?

ADAMTSL4 p.Pro620= (c.1860G>A) is associated with ectopia lentis et pupillae, ectopia lentis 2, isolated, autosomal recessive (ClinVar).

How common is ADAMTSL4 p.Pro620= (c.1860G>A) in the general population?

ADAMTSL4 p.Pro620= (c.1860G>A) is very rare (popmax 0.00803%, afr) (gnomAD).

ADAMTSL4 p.Pro620=

c.1860G>A · rs754436821 · VCV292539

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00803%, afr)

Conditions

ectopia lentis et pupillae

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 -4.1
Overall
CADD	0.174	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00803% African / African-American · 6/74,726 alleles

Filtering AF 0.00348% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.00155% 25/1,610,874 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00803%	12,454
Remaining individualsnot grpmax-eligible	0.00803%	12,461
East Asian	0.00671%	14,896
European (non-Finnish)	0.000933%	107,138

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: ADAMTSL4
Protein: p.Pro620=
Coding: c.1860G>A
MANE Select: NM_019032
dbSNP: rs754436821
Type: single nucleotide variant
Location: chr1:150557049 (GRCh38)
Gene constraint: LOEUF 0.92 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.18

Full ADAMTSL4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ectopia lentis et pupillae — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ectopia lentis 2, isolated, autosomal recessive

Similar variants

ADAMTSL4 p.Pro620Leu Uncertain significance ★★ ⚠ same residue
ADAMTSL4 c.2178-2A>G Likely pathogenic ★★ same condition
ADAMTSL4 p.Arg1007Ter Pathogenic/Likely pathogenic ★★ same condition
ADAMTSL4 p.Arg141Ter Pathogenic ★★ same condition
ADAMTSL4 p.Arg670Ter Pathogenic/Likely pathogenic ★★ same condition
ADAMTSL4 p.Arg746His Pathogenic ★★ same condition
ADAMTSL4 p.Arg865His Pathogenic/Likely pathogenic ★★ same condition
ADAMTSL4 p.Cys799Ter 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/adamtsl4-p-pro620 (accessed [today's date]).

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