Is INTS11 p.Ser532Asn (c.1595G>A) pathogenic?

INTS11 p.Ser532Asn (c.1595G>A) is classified Uncertain significance in INTS11 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-18). AlphaMissense: likely benign (0.0848); Very rare (popmax 0.00964%, eas).

How common is INTS11 p.Ser532Asn (c.1595G>A) in the general population?

INTS11 p.Ser532Asn (c.1595G>A) is very rare (popmax 0.00964%, eas) (gnomAD).

What do computational predictors say about INTS11 p.Ser532Asn (c.1595G>A)?

AlphaMissense predicts likely benign (score 0.0848) — an in-silico prediction, not a clinical call.

INTS11 p.Ser532Asn

c.1595G>A · rs1179153155 · VCV3110097

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0848 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00964%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0848	likely benign
REVEL	0.086	moderately benign-leaning
SaProt	LLR -5.85	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.2	GERP 0.9, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 13 kb · p 0.087 · regional, not allelic
Overall
CADD	17.09	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 0.00964% East Asian · 4/41,514 alleles

Filtering AF 0.00325% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00191%

Overall 0.000743% 11/1,480,096 alleles · very rare exomes 9/1,353,608 · genomes 2/126,488 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00964%	10,379
Ashkenazi Jewishnot grpmax-eligible	0.00365%	27,366
Remaining individualsnot grpmax-eligible	0.00173%	57,912
European (non-Finnish)	0.000455%	219,542

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: INTS11
Protein: p.Ser532Asn
Coding: c.1595G>A
MANE Select: NM_017871
dbSNP: rs1179153155
Type: single nucleotide variant
Location: chr1:1312238 (GRCh38)
Gene constraint: LOEUF 1.223 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.82 · 15 PDB
Residue 532: an α-helix

Full INTS11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

INTS11 c.28+1406C>T Uncertain significance ★★ same type
INTS11 p.Ala241Thr Uncertain significance ★★ ⚠ same type
INTS11 p.Arg231Cys Uncertain significance ★★ ⚠ same type
INTS11 p.Gln467His Uncertain significance ★★ ⚠ same type
INTS11 p.Glu227Lys Uncertain significance ★★ same type
INTS11 p.His157Arg Uncertain significance ★★ ⚠ same type
INTS11 c.1607+18C>A Benign ★★ same type
INTS11 p.Arg196= Benign ★★ 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/ints11-p-ser532asn (accessed [today's date]).

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