Is ADSS2 p.Asp78Glu (c.234T>G) pathogenic?

ADSS2 p.Asp78Glu (c.234T>G) is classified Uncertain significance in ADSS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-09). AlphaMissense: likely pathogenic (0.9007); Ultra-rare (popmax 0.0182%, nfe).

How common is ADSS2 p.Asp78Glu (c.234T>G) in the general population?

ADSS2 p.Asp78Glu (c.234T>G) is ultra-rare (popmax 0.0182%, nfe) (gnomAD).

What do computational predictors say about ADSS2 p.Asp78Glu (c.234T>G)?

AlphaMissense predicts likely pathogenic (score 0.9007) — an in-silico prediction, not a clinical call.

ADSS2 p.Asp78Glu

c.234T>G · rs139290156 · VCV3091344

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9007 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0182%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9007	likely pathogenic
REVEL	0.157	moderately benign-leaning
SaProt	LLR -11.99	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -3.2, phastCons 1
Regional constraint	o/e 0.40	unconstrained · MANE · 14 kb · p 2.3e-07 · regional, not allelic
Overall
CADD	21.2	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 0.0182% European (non-Finnish) · 214/1,175,396 alleles

Filtering AF 0.0162% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0154%

Overall 0.0135% 217/1,608,770 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0182%	5,493
Remaining individualsnot grpmax-eligible	0.0016%	62,326
African / African-American	0.00133%	74,912
South Asian	0.0011%	90,950

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: ADSS2
Protein: p.Asp78Glu
Coding: c.234T>G
MANE Select: NM_001126
dbSNP: rs139290156
Type: single nucleotide variant
Location: chr1:244437718 (GRCh38)
Gene constraint: LOEUF 0.646 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 92.90 · 1 PDB
Residue 78: a β-strand

Full ADSS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADSS2 p.Ala349Thr Uncertain significance ★ ⚠ same type
ADSS2 p.Ala390Val Uncertain significance ★ ⚠ same type
ADSS2 p.Ala417Ser Uncertain significance ★ ⚠ same type
ADSS2 p.Ala417Val Uncertain significance ★ ⚠ same type
ADSS2 p.Asn409Lys Uncertain significance ★ ⚠ same type
ADSS2 p.Asn90Lys Uncertain significance ★ ⚠ same type
ADSS2 p.Asp17Asn Uncertain significance ★ ⚠ same type
ADSS2 p.Asp381Asn Uncertain significance ★ ⚠ 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/adss2-p-asp78glu (accessed [today's date]).

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