Is ARSG p.Ser69Leu (c.206C>T) pathogenic?

ARSG p.Ser69Leu (c.206C>T) is classified Uncertain significance in ARSG (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-31). AlphaMissense: likely benign (0.0802); Ultra-rare (popmax 0.0179%, mid).

How common is ARSG p.Ser69Leu (c.206C>T) in the general population?

ARSG p.Ser69Leu (c.206C>T) is ultra-rare (popmax 0.0179%, mid) (gnomAD).

What do computational predictors say about ARSG p.Ser69Leu (c.206C>T)?

AlphaMissense predicts likely benign (score 0.0802) — an in-silico prediction, not a clinical call.

ARSG p.Ser69Leu

c.206C>T · rs1369350242 · VCV1521634

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0802 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0179%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0802	likely benign
REVEL	0.159	moderately benign-leaning
SaProt	LLR -7.63	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.4	GERP -0.28, phastCons 0.001
Regional constraint	o/e 0.93	unconstrained · MANE · 113 kb · p 0.075 · regional, not allelic
Overall
CADD	16.3	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 0.0179% Middle Eastern · 1/5,590 alleles

Filtering AF 0.000368% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000138%

Overall 0.000381% 6/1,575,390 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0179%	5,590
South Asian	0.00221%	45,167
Finnishnot grpmax-eligible	0.00156%	64,008
European (non-Finnish)	0.000175%	572,577

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.Ser69Leu
Coding: c.206C>T
MANE Select: NM_001267727
dbSNP: rs1369350242
Type: single nucleotide variant
Location: chr17:68307699 (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.Ser69= 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.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-ser69leu (accessed [today's date]).

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