Is ADSL p.Phe232Val (c.694T>G) pathogenic?

ADSL p.Phe232Val (c.694T>G) is classified Uncertain significance in ADSL (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-02). AlphaMissense: likely pathogenic (0.9742); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ADSL p.Phe232Val (c.694T>G)?

ADSL p.Phe232Val (c.694T>G) is associated with Inborn genetic diseases (ClinVar).

How common is ADSL p.Phe232Val (c.694T>G) in the general population?

ADSL p.Phe232Val (c.694T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADSL p.Phe232Val (c.694T>G)?

AlphaMissense predicts likely pathogenic (score 0.9742) — an in-silico prediction, not a clinical call.

ADSL p.Phe232Val

c.694T>G · rs2518113206 · VCV2275032

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9742 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9742	likely pathogenic
REVEL	0.89	moderately pathogenic-leaning
SaProt	LLR -14.29	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 7.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 20 kb · p 5.6e-07 · regional, not allelic
Overall
CADD	29.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ADSL
Protein: p.Phe232Val
Coding: c.694T>G
MANE Select: NM_000026
dbSNP: rs2518113206
Type: single nucleotide variant
Location: chr22:40359299 (GRCh38)
Gene constraint: LOEUF 0.915 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.82 · 4 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ADSL c.-49T>C Pathogenic/Likely pathogenic ★★ same condition
ADSL p.Ala103Ser Uncertain significance ★★ ⚠ same condition
ADSL p.Ala480Gly Uncertain significance ★★ ⚠ same condition
ADSL p.Arg196Gln Uncertain significance ★★ ⚠ same condition
ADSL p.Arg309Cys Uncertain significance ★★ ⚠ same condition
ADSL p.Arg372His Uncertain significance ★★ ⚠ same condition
ADSL p.Asn126Ser Uncertain significance ★★ ⚠ same condition
ADSL p.Asn421Ser Uncertain significance ★★ ⚠ 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/adsl-p-phe232val (accessed [today's date]).

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