Is ARSL p.Phe243Ser (c.728T>C) pathogenic?

ARSL p.Phe243Ser (c.728T>C) is classified Conflicting classifications of pathogenicity in ARSL (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-12-22). AlphaMissense: likely benign (0.1356); Ultra-rare (popmax 0.019%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ARSL p.Phe243Ser (c.728T>C)?

ARSL p.Phe243Ser (c.728T>C) is associated with Inborn genetic diseases, chondrodysplasia punctata, brachytelephalangic, autosomal (ClinVar).

How common is ARSL p.Phe243Ser (c.728T>C) in the general population?

ARSL p.Phe243Ser (c.728T>C) is ultra-rare (popmax 0.019%, nfe) (gnomAD).

What do computational predictors say about ARSL p.Phe243Ser (c.728T>C)?

AlphaMissense predicts likely benign (score 0.1356) — an in-silico prediction, not a clinical call.

ARSL p.Phe243Ser

c.728T>C · rs779527848 · VCV1683197

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1356 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.019%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1356	likely benign
REVEL	0.197	benign-leaning
SaProt	LLR -7.10	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.5	GERP 0.29
Regional constraint	o/e 0.63	unconstrained · MANE · 26 kb · p 8.2e-17 · regional, not allelic
Overall
CADD	1.438	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 0.019% European (non-Finnish) · 170/895,028 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0157%

Overall 0.0142% 172/1,208,795 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.019%	5,265
Remaining individualsnot grpmax-eligible	0.0042%	23,790

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.Phe243Ser
Coding: c.728T>C
MANE Select: NM_000047
dbSNP: rs779527848
Type: single nucleotide variant
Location: chrX:2949430 (GRCh38)
Structure: AlphaFold pLDDT 92.57

Full ARSL 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

Also linked: chondrodysplasia punctata, brachytelephalangic, autosomal

Similar variants

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
ARSL p.Asp413Glu 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-phe243ser (accessed [today's date]).

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