Is ARSG p.Asp65Glu (c.195T>A) pathogenic?

ARSG p.Asp65Glu (c.195T>A) is classified Uncertain significance in ARSG (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-08). AlphaMissense: ambiguous (0.4255); Very rare (popmax 0.00552%, nfe).

How common is ARSG p.Asp65Glu (c.195T>A) in the general population?

ARSG p.Asp65Glu (c.195T>A) is very rare (popmax 0.00552%, nfe) (gnomAD).

What do computational predictors say about ARSG p.Asp65Glu (c.195T>A)?

AlphaMissense predicts ambiguous (score 0.4255) — an in-silico prediction, not a clinical call.

ARSG p.Asp65Glu

c.195T>A · rs138635679 · VCV855006

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4255 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00552%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4255	ambiguous
REVEL	0.366	indeterminate
SaProt	LLR -10.75	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.32	GERP -0.45, phastCons 0.001
Regional constraint	o/e 0.93	unconstrained · MANE · 113 kb · p 0.075 · regional, not allelic
Overall
CADD	21.6	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 0.00552% European (non-Finnish) · 64/1,160,356 alleles

Filtering AF 0.00442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00402%

Overall 0.00433% 69/1,592,292 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00552%	18,131
African / African-American	0.00537%	18,621
Remaining individualsnot grpmax-eligible	0.00162%	61,742

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.Asp65Glu
Coding: c.195T>A
MANE Select: NM_001267727
dbSNP: rs138635679
Type: single nucleotide variant
Location: chr17:68307688 (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

WIPI1 p.Arg65His Uncertain significance ★ ⚠ 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.Ala313Val Uncertain significance ★★ ⚠ same type
ARSG p.Ala374Pro Uncertain significance ★★ ⚠ same type
ARSG p.Ala437Val 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-asp65glu (accessed [today's date]).

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