Is ADSL p.Thr38Arg (c.113C>G) pathogenic?

ADSL p.Thr38Arg (c.113C>G) is classified Uncertain significance in ADSL (ClinVar, Single submitter, 1 submitter; last evaluated 2017-07-25). AlphaMissense: likely pathogenic (0.684); Very rare (popmax 8.48e-05%, nfe).

How common is ADSL p.Thr38Arg (c.113C>G) in the general population?

ADSL p.Thr38Arg (c.113C>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about ADSL p.Thr38Arg (c.113C>G)?

AlphaMissense predicts likely pathogenic (score 0.684) — an in-silico prediction, not a clinical call.

ADSL p.Thr38Arg

c.113C>G · rs747976292 · VCV204810

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.684 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.684	likely pathogenic
REVEL	0.941	strongly pathogenic-leaning
SaProt	LLR -13.77	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 20 kb · p 5.6e-07 · regional, not allelic
Overall
CADD	28.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,724 alleles

Overall 6.85e-05% 1/1,460,554 alleles · very rare

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: ADSL
Protein: p.Thr38Arg
Coding: c.113C>G
MANE Select: NM_000026
dbSNP: rs747976292
Type: single nucleotide variant
Location: chr22:40346671 (GRCh38)
Gene constraint: LOEUF 0.915 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.82 · 4 PDB
Residue 38: an α-helix

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

Similar variants

ADSL p.Thr38= Likely benign ★★ same residue
ADSL c.1191+5G>C Pathogenic/Likely pathogenic ★★ same type
ADSL c.402+1G>T Likely pathogenic ★★ same type
ADSL c.482+1G>C Likely pathogenic ★★ same type
ADSL c.-49T>C Pathogenic/Likely pathogenic ★★ same type
ADSL p.Arg141Trp Pathogenic/Likely pathogenic ★★ same type
ADSL p.Arg149Ter Pathogenic/Likely pathogenic ★★ same type
ADSL p.Arg190Gln Pathogenic/Likely 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/adsl-p-thr38arg (accessed [today's date]).

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