Is INTS11 p.Val551fs (c.1652_1653del) pathogenic?

INTS11 p.Val551fs (c.16521653del) is classified Likely pathogenic in INTS11 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-04-17). Very rare (popmax 0.00115%, sas); Associated with neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities.

How common is INTS11 p.Val551fs (c.1652_1653del) in the general population?

INTS11 p.Val551fs (c.1652_1653del) is very rare (popmax 0.00115%, sas) (gnomAD).

INTS11 p.Val551fs

Q: What condition is associated with INTS11 p.Val551fs (c.1652_1653del)?

INTS11 p.Val551fs (c.1652_1653del) is associated with neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities (ClinVar).

c.1652_1653del · VCV3359221

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00115%, sas)

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 16 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00115% South Asian · 1/86,848 alleles

Filtering AF 6.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000317% 5/1,576,126 alleles · very rare exomes 5/1,426,566 · genomes 0/149,560 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00164%	61,064
South Asiangrpmax	0.00115%	86,848
European (non-Finnish)	0.000259%	386,716

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val551fs
Coding: c.1652_1653del
MANE Select: NM_017871
Type: Microsatellite
Location: chr1:1312102 (GRCh38)
Gene constraint: LOEUF 1.223 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.82 · 15 PDB
Residue 551: a β-strand; a UniProt-annotated variant site (in nedmlob; uncertain significance)

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 p.Val551Glu Likely pathogenic same residue
INTS11 p.Arg521fs Likely pathogenic ★ same condition
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

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-val551fs (accessed [today's date]).

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