Is INTS6 p.Ala530Ser (c.1588G>T) pathogenic?

INTS6 p.Ala530Ser (c.1588G>T) is classified Uncertain significance in INTS6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-22). AlphaMissense: likely benign (0.141); Very rare (popmax 8.48e-05%, nfe).

How common is INTS6 p.Ala530Ser (c.1588G>T) in the general population?

INTS6 p.Ala530Ser (c.1588G>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about INTS6 p.Ala530Ser (c.1588G>T)?

AlphaMissense predicts likely benign (score 0.141) — an in-silico prediction, not a clinical call.

INTS6 p.Ala530Ser

c.1588G>T · VCV4679154

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.141 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.141	likely benign
REVEL	0.273	benign-leaning
SaProt	LLR -5.43	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 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 13 kb · p 1.5e-11 · regional, not allelic
Overall
CADD	25.9	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 8.48e-05% European (non-Finnish) · 1/1,178,592 alleles

Overall 6.2e-05% 1/1,612,246 alleles · very rare exomes 0/1,460,230 · genomes 1/152,016 · joint denominator

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: INTS6
Protein: p.Ala530Ser
Coding: c.1588G>T
MANE Select: NM_012141
Type: single nucleotide variant
Location: chr13:51378253 (GRCh38)
Gene constraint: LOEUF 0.23 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.80 · 9 PDB

Full INTS6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

INTS6 p.Thr749Ala Benign ★★ same type
INTS6 p.Arg206Cys Likely pathogenic ★ same type
INTS6 p.Arg610Ter Pathogenic ★ same type
INTS6 p.Gln185Ter Pathogenic ★ same type
INTS6 p.Gln228Glu Likely pathogenic ★ same type
INTS6 c.613+2T>C Uncertain significance ★ same type
INTS6 p.Ala44Gly Uncertain significance ★ ⚠ same type
INTS6 p.Ala742Thr 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/ints6-p-ala530ser (accessed [today's date]).

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