Is ARSL p.Val74Met (c.220G>A) pathogenic?

ARSL p.Val74Met (c.220G>A) is classified Benign in ARSL (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-04). AlphaMissense: likely benign (0.1999); Low-frequency (popmax 3.11%, eas); Associated with chondrodysplasia punctata, brachytelephalangic, autosomal.

What condition is associated with ARSL p.Val74Met (c.220G>A)?

ARSL p.Val74Met (c.220G>A) is associated with chondrodysplasia punctata, brachytelephalangic, autosomal (ClinVar).

How common is ARSL p.Val74Met (c.220G>A) in the general population?

ARSL p.Val74Met (c.220G>A) is low-frequency (popmax 3.11%, eas) (gnomAD).

What do computational predictors say about ARSL p.Val74Met (c.220G>A)?

AlphaMissense predicts likely benign (score 0.1999) — an in-silico prediction, not a clinical call.

ARSL p.Val74Met

c.220G>A · rs150756612 · VCV772428

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1999 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.11%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

chondrodysplasia punctata, brachytelephalangic, autosomal

Computational evidence

Protein change
AlphaMissense	0.1999	likely benign
REVEL	0.591	indeterminate
SaProt	LLR -11.19	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.9	GERP 0.23, phastCons 0.45
Regional constraint	o/e 0.63	unconstrained · MANE · 26 kb · p 8.2e-17 · regional, not allelic
Overall
CADD	17.13	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 3.11% East Asian · 1,051/33,744 alleles

Filtering AF 2.96% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.9%

Overall 0.093% 1,125/1,209,533 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	3.11%	32
Remaining individualsnot grpmax-eligible	0.042%	2,381
African / African-American	0.014%	7,155
European (non-Finnish)	0.00492%	20,340
Admixed American	0.00438%	22,848

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: ARSL
Protein: p.Val74Met
Coding: c.220G>A
MANE Select: NM_000047
dbSNP: rs150756612
Type: single nucleotide variant
Location: chrX:2955503 (GRCh38)
Structure: AlphaFold pLDDT 92.57

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

Disease context

chondrodysplasia punctata, brachytelephalangic, autosomal — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ARSL p.Val74= Likely benign ★ same residue
ARSL c.24-2A>G Likely pathogenic ★★ same condition
ARSL p.Gly73Ser Likely pathogenic ★★ ⚠ same condition
ARSL p.Ala182Thr Uncertain significance ★★ ⚠ same condition
ARSL p.Ala251Val Uncertain significance ★★ ⚠ same condition
ARSL p.Ala45Val Uncertain significance ★★ ⚠ same condition
ARSL p.Arg12Ser Uncertain significance ★★ ⚠ same condition
ARSL p.Arg190His 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/arsl-p-val74met (accessed [today's date]).

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