Is ADAMTSL4 p.Arg710Ser (c.2130G>T) pathogenic?

ADAMTSL4 p.Arg710Ser (c.2130G>T) is classified Likely benign in ADAMTSL4 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-17). AlphaMissense: ambiguous (0.3782); Very rare (popmax 0.00391%, nfe).

How common is ADAMTSL4 p.Arg710Ser (c.2130G>T) in the general population?

ADAMTSL4 p.Arg710Ser (c.2130G>T) is very rare (popmax 0.00391%, nfe) (gnomAD).

What do computational predictors say about ADAMTSL4 p.Arg710Ser (c.2130G>T)?

AlphaMissense predicts ambiguous (score 0.3782) — an in-silico prediction, not a clinical call.

ADAMTSL4 p.Arg710Ser

c.2130G>T · rs202093883 · VCV1938895

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3782 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00391%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3782	ambiguous
REVEL	0.234	benign-leaning
SaProt	LLR -10.35	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -3.5, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 7,904 bp · p 0.23 · regional, not allelic
Overall
CADD	19.01	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00391% European (non-Finnish) · 46/1,176,170 alleles

Filtering AF 0.003% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00268%

Overall 0.016% 256/1,604,436 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.318%	315
Remaining individualsnot grpmax-eligible	0.0209%	4,775
European (non-Finnish)grpmax	0.00391%	25,569

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg710Ser
Coding: c.2130G>T
MANE Select: NM_019032
dbSNP: rs202093883
Type: single nucleotide variant
Location: chr1:150557576 (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

Similar variants

ADAMTSL4 p.Arg710= Likely benign ★ same residue
ADAMTSL4 c.2178-2A>G Likely pathogenic ★★ same type
ADAMTSL4 p.Arg1007Ter Pathogenic/Likely pathogenic ★★ same type
ADAMTSL4 p.Arg126Ter Pathogenic/Likely pathogenic ★★ same type
ADAMTSL4 p.Arg141Ter Pathogenic ★★ same type
ADAMTSL4 p.Arg309Ter Pathogenic ★★ same type
ADAMTSL4 p.Arg670Ter Pathogenic/Likely pathogenic ★★ same type
ADAMTSL4 p.Arg746His 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/adamtsl4-p-arg710ser (accessed [today's date]).

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