Is ATMIN p.Ser573Thr (c.1718G>C) pathogenic?

ATMIN p.Ser573Thr (c.1718G>C) is classified Uncertain significance in ATMIN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: likely benign (0.0795); Ultra-rare (popmax 0.0154%, sas).

How common is ATMIN p.Ser573Thr (c.1718G>C) in the general population?

ATMIN p.Ser573Thr (c.1718G>C) is ultra-rare (popmax 0.0154%, sas) (gnomAD).

What do computational predictors say about ATMIN p.Ser573Thr (c.1718G>C)?

AlphaMissense predicts likely benign (score 0.0795) — an in-silico prediction, not a clinical call.

ATMIN p.Ser573Thr

c.1718G>C · rs144895396 · VCV2406953

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0795 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0154%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0795	likely benign
REVEL	0.102	moderately benign-leaning
SaProt	LLR -6.95	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 2.5	GERP 2.6, phastCons 0.063
Regional constraint	o/e 1.03	unconstrained · MANE · 9,096 bp · p 0.32 · regional, not allelic
Overall
CADD	11.35	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 0.0154% South Asian · 14/91,084 alleles

Filtering AF 0.00919% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00735%

Overall 0.0018% 29/1,614,012 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0154%	6,506
East Asian	0.00668%	14,965
Remaining individualsnot grpmax-eligible	0.0064%	15,622
European (non-Finnish)	0.000678%	147,502

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: ATMIN
Protein: p.Ser573Thr
Coding: c.1718G>C
MANE Select: NM_015251
dbSNP: rs144895396
Type: single nucleotide variant
Location: chr16:81044216 (GRCh38)
Gene constraint: LOEUF 0.695 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 47.67

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

Similar variants

ATMIN p.Ala10Glu Uncertain significance ★ ⚠ same type
ATMIN p.Ala16Val Uncertain significance ★ ⚠ same type
ATMIN p.Ala19Gly Uncertain significance ★ ⚠ same type
ATMIN p.Ala302Val Uncertain significance ★ ⚠ same type
ATMIN p.Ala340Thr Uncertain significance ★ ⚠ same type
ATMIN p.Ala359Thr Uncertain significance ★ ⚠ same type
ATMIN p.Ala3Gly Uncertain significance ★ ⚠ same type
ATMIN p.Ala431Thr 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/atmin-p-ser573thr (accessed [today's date]).

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