Is ARSJ p.Val174Ile (c.520G>A) pathogenic?

ARSJ p.Val174Ile (c.520G>A) is classified Uncertain significance in ARSJ (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-14). AlphaMissense: likely benign (0.1062); Ultra-rare (popmax 0.0826%, afr).

How common is ARSJ p.Val174Ile (c.520G>A) in the general population?

ARSJ p.Val174Ile (c.520G>A) is ultra-rare (popmax 0.0826%, afr) (gnomAD).

What do computational predictors say about ARSJ p.Val174Ile (c.520G>A)?

AlphaMissense predicts likely benign (score 0.1062) — an in-silico prediction, not a clinical call.

ARSJ p.Val174Ile

c.520G>A · rs181598203 · VCV2391983

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1062 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0826%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1062	likely benign
REVEL	0.59	indeterminate
SaProt	LLR -7.17	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.5, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 77 kb · p 0.035 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0826% African / African-American · 62/75,046 alleles

Filtering AF 0.0661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0602%

Overall 0.0044% 71/1,614,162 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0826%	1,210
Remaining individualsnot grpmax-eligible	0.0064%	15,626
Admixed American	0.005%	20,007
European (non-Finnish)	0.000169%	590,009

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: ARSJ
Protein: p.Val174Ile
Coding: c.520G>A
MANE Select: NM_024590
dbSNP: rs181598203
Type: single nucleotide variant
Location: chr4:113903554 (GRCh38)
Gene constraint: LOEUF 0.951 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.34

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

Similar variants

ARSJ p.Ala107Thr Uncertain significance ★ ⚠ same type
ARSJ p.Ala295Ser Uncertain significance ★ ⚠ same type
ARSJ p.Ala444Pro Uncertain significance ★ ⚠ same type
ARSJ p.Ala7Glu Uncertain significance ★ ⚠ same type
ARSJ p.Arg283Gln Uncertain significance ★ ⚠ same type
ARSJ p.Arg283Leu Uncertain significance ★ ⚠ same type
ARSJ p.Arg479Pro Uncertain significance ★ ⚠ same type
ARSJ p.Arg511Lys 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/arsj-p-val174ile (accessed [today's date]).

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