Is INTS11 p.Ala313fs (c.936dup) pathogenic?

INTS11 p.Ala313fs (c.936dup) is classified Conflicting classifications of pathogenicity in INTS11 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-02-13). Ultra-rare (popmax 0.0162%, nfe); Associated with neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities.

How common is INTS11 p.Ala313fs (c.936dup) in the general population?

INTS11 p.Ala313fs (c.936dup) is ultra-rare (popmax 0.0162%, nfe) (gnomAD).

INTS11 p.Ala313fs

Q: What condition is associated with INTS11 p.Ala313fs (c.936dup)?

INTS11 p.Ala313fs (c.936dup) is associated with neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities (ClinVar).

c.936dup · rs556125116 · VCV3236609

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0162%, nfe)

Conditions

neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.9	GERP 0.86, phastCons 1
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0162% European (non-Finnish) · 191/1,179,926 alleles

Filtering AF 0.0143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.0122% 196/1,613,088 alleles · ultra-rare exomes 179/1,460,712 · genomes 17/152,376 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0162%	6,178
African / African-American	0.004%	25,024
Remaining individualsnot grpmax-eligible	0.0032%	31,244

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.Ala313fs
Coding: c.936dup
MANE Select: NM_017871
dbSNP: rs556125116
Type: Duplication
Location: chr1:1313752 (GRCh38)
Gene constraint: LOEUF 1.223 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.82 · 15 PDB
Residue 313: an α-helix

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

Disease context

neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

INTS11 c.28+1406C>T Uncertain significance ★★ same condition
INTS11 p.Arg231Cys Uncertain significance ★★ ⚠ same condition
INTS11 p.Glu227Lys Uncertain significance ★★ same condition
INTS11 c.1738-1G>A Likely pathogenic ★ same condition
INTS11 p.Arg17Leu Pathogenic ★ same condition
INTS11 p.Arg43Ter Pathogenic ★ same condition
INTS11 p.Arg521fs Likely pathogenic ★ same condition
INTS11 p.Glu171fs Likely pathogenic ★ same condition

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-ala313fs (accessed [today's date]).

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