Is ATOSB p.Ser319Arg (c.957C>A) pathogenic?

ATOSB p.Ser319Arg (c.957C>A) is classified Uncertain significance in ATOSB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-16). AlphaMissense: likely benign (0.3002); Ultra-rare (popmax 0.0119%, sas).

How common is ATOSB p.Ser319Arg (c.957C>A) in the general population?

ATOSB p.Ser319Arg (c.957C>A) is ultra-rare (popmax 0.0119%, sas) (gnomAD).

What do computational predictors say about ATOSB p.Ser319Arg (c.957C>A)?

AlphaMissense predicts likely benign (score 0.3002) — an in-silico prediction, not a clinical call.

ATOSB p.Ser319Arg

c.957C>A · rs745611217 · VCV3131208

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3002 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0119%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3002	likely benign
REVEL	0.368	indeterminate
SaProt	LLR -7.00	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.22	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 3.5	GERP 1.7, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 1,701 bp · p 0.96 · regional, not allelic
Overall
CADD	14.65	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 0.0119% South Asian · 10/84,166 alleles

Filtering AF 0.00639% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00486%

Overall 0.00284% 44/1,549,586 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0119%	8,417
European (non-Finnish)	0.00288%	34,700
African / African-American	0.00137%	73,066

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: ATOSB
Protein: p.Ser319Arg
Coding: c.957C>A
MANE Select: NM_025182
dbSNP: rs745611217
Type: single nucleotide variant
Location: chr9:35106640 (GRCh38)
Structure: AlphaFold pLDDT 56.25

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

Similar variants

ATOSB p.Ala161Val Uncertain significance ★ ⚠ same type
ATOSB p.Ala194Thr Uncertain significance ★ ⚠ same type
ATOSB p.Ala220Thr Uncertain significance ★ ⚠ same type
ATOSB p.Ala27Ser Uncertain significance ★ ⚠ same type
ATOSB p.Ala6Val Uncertain significance ★ ⚠ same type
ATOSB p.Arg263Gln Uncertain significance ★ ⚠ same type
ATOSB p.Arg263Trp Uncertain significance ★ ⚠ same type
ATOSB p.Arg265His 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/atosb-p-ser319arg (accessed [today's date]).

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