Is ARSG p.Ala313Val (c.938C>T) pathogenic?

ARSG p.Ala313Val (c.938C>T) is classified Uncertain significance in ARSG (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-10-12). AlphaMissense: ambiguous (0.4885); Very rare (popmax 0.00223%, eas).

How common is ARSG p.Ala313Val (c.938C>T) in the general population?

ARSG p.Ala313Val (c.938C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about ARSG p.Ala313Val (c.938C>T)?

AlphaMissense predicts ambiguous (score 0.4885) — an in-silico prediction, not a clinical call.

ARSG p.Ala313Val

c.938C>T · rs374175059 · VCV1389533

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4885 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4885	ambiguous
REVEL	0.744	pathogenic-leaning
SaProt	LLR -10.38	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.8, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 113 kb · p 0.075 · regional, not allelic
Overall
CADD	25.1	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 0.00223% East Asian · 1/44,870 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000744% 12/1,613,976 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,870
Admixed American	0.00167%	60,002
Remaining individualsnot grpmax-eligible	0.0016%	62,508
African / African-American	0.00133%	74,994
European (non-Finnish)	0.000678%	147,494

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: ARSG
Protein: p.Ala313Val
Coding: c.938C>T
MANE Select: NM_001267727
dbSNP: rs374175059
Type: single nucleotide variant
Location: chr17:68370480 (GRCh38)
Gene constraint: LOEUF 0.996 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.90

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

Similar variants

ARSG p.Ala313= Likely benign ★ same residue
ARSG c.1091+1G>A Likely pathogenic ★★ same type
ARSG c.982+2T>G Likely pathogenic ★★ same type
ARSG p.Ala180Val Uncertain significance ★★ ⚠ same type
ARSG p.Ala262Val Uncertain significance ★★ ⚠ same type
ARSG p.Ala374Pro Uncertain significance ★★ ⚠ same type
ARSG p.Ala437Val Uncertain significance ★★ ⚠ same type
ARSG p.Ala473Val 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/arsg-p-ala313val (accessed [today's date]).

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