Is DIS3L2 p.Ser173= (c.519C>T) pathogenic?

DIS3L2 p.Ser173= (c.519C>T) is classified Conflicting classifications of pathogenicity in DIS3L2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-10). Rare (popmax 0.192%, eas); Associated with Perlman syndrome.

What condition is associated with DIS3L2 p.Ser173= (c.519C>T)?

DIS3L2 p.Ser173= (c.519C>T) is associated with Perlman syndrome (ClinVar).

How common is DIS3L2 p.Ser173= (c.519C>T) in the general population?

DIS3L2 p.Ser173= (c.519C>T) is rare (popmax 0.192%, eas) (gnomAD).

DIS3L2 p.Ser173=

c.519C>T · rs143680532 · VCV334931

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.192%, eas)

Conditions

Perlman syndrome

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 -10	GERP -3.6
Overall
CADD	4.212	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.192% East Asian · 86/44,874 alleles

Filtering AF 0.159% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.147%

Overall 0.0062% 100/1,614,048 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.192%	522
Admixed American	0.00333%	30,005
Remaining individualsnot grpmax-eligible	0.0032%	31,253
African / African-American	0.00133%	74,980
European (non-Finnish)	0.000763%	131,114

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: DIS3L2
Protein: p.Ser173=
Coding: c.519C>T
MANE Select: NM_152383
dbSNP: rs143680532
Type: single nucleotide variant
Location: chr2:232087639 (GRCh38)
Gene constraint: LOEUF 0.468 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 83.26 · 4 PDB
Residue 173: a modified residue (phosphoserine)

Full DIS3L2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Perlman syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DIS3L2 c.1740-1G>C Likely pathogenic ★★ same condition
DIS3L2 p.Arg245Ter Pathogenic/Likely pathogenic ★★ same condition
DIS3L2 p.Arg388Ter Pathogenic/Likely pathogenic ★★ same condition
DIS3L2 p.Arg43Ter Pathogenic/Likely pathogenic ★★ same condition
DIS3L2 p.Arg724Ter Pathogenic/Likely pathogenic ★★ same condition
DIS3L2 p.Gln604Ter Pathogenic ★★ same condition
DIS3L2 p.Glu332Ter Likely pathogenic ★★ same condition
DIS3L2 p.Glu366Ter Pathogenic/Likely 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/dis3l2-p-ser173 (accessed [today's date]).

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