Is ARSG p.Pro177Ser (c.529C>T) pathogenic?

ARSG p.Pro177Ser (c.529C>T) is classified Conflicting classifications of pathogenicity in ARSG (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-01-15). AlphaMissense: likely benign (0.0866); Rare (popmax 0.168%, amr).

How common is ARSG p.Pro177Ser (c.529C>T) in the general population?

ARSG p.Pro177Ser (c.529C>T) is rare (popmax 0.168%, amr) (gnomAD).

What do computational predictors say about ARSG p.Pro177Ser (c.529C>T)?

AlphaMissense predicts likely benign (score 0.0866) — an in-silico prediction, not a clinical call.

ARSG p.Pro177Ser

c.529C>T · rs150020444 · VCV853466

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0866 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.168%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0866	likely benign
REVEL	0.095	moderately benign-leaning
SaProt	LLR -6.61	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 4.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 113 kb · p 0.075 · regional, not allelic
Overall
CADD	20.6	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 0.168% Admixed American · 101/60,012 alleles

Filtering AF 0.142% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.132%

Overall 0.0563% 909/1,613,886 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.168%	594
South Asian	0.067%	1,493
Middle Eastern	0.066%	1,516
European (non-Finnish)	0.0571%	1,750
Remaining individualsnot grpmax-eligible	0.0496%	2,016
Finnishnot grpmax-eligible	0.0281%	3,556
Ashkenazi Jewishnot grpmax-eligible	0.0236%	4,229
African / African-American	0.0173%	5,771

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.Pro177Ser
Coding: c.529C>T
MANE Select: NM_001267727
dbSNP: rs150020444
Type: single nucleotide variant
Location: chr17:68351649 (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 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
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-pro177ser (accessed [today's date]).

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