Is INTS11 p.Val551Glu (c.1652T>A) pathogenic?

INTS11 p.Val551Glu (c.1652T>A) is classified Likely pathogenic in INTS11 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-04-17). AlphaMissense: likely pathogenic (0.9873); No allele count reported in gnomAD v4.1 (AN 1,575,472); Associated with neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities.

How common is INTS11 p.Val551Glu (c.1652T>A) in the general population?

INTS11 p.Val551Glu (c.1652T>A) is no allele count reported in gnomAD v4.1 (AN 1,575,472) (gnomAD).

What do computational predictors say about INTS11 p.Val551Glu (c.1652T>A)?

AlphaMissense predicts likely pathogenic (score 0.9873) — an in-silico prediction, not a clinical call.

INTS11 p.Val551Glu

Q: What condition is associated with INTS11 p.Val551Glu (c.1652T>A)?

INTS11 p.Val551Glu (c.1652T>A) is associated with neurodevelopmental disorder with motor and language delay, ocular defects, and brain abnormalities (ClinVar).

c.1652T>A · VCV3359222

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9873 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,575,472)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

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

Computational evidence

Protein change
AlphaMissense	0.9873	likely pathogenic ✓ concordant with ClinVar
REVEL	0.327	indeterminate
SaProt	LLR -15.57	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.24	acceptor loss, 26 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 13 kb · p 0.087 · regional, not allelic
Overall
CADD	22.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,575,472). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: INTS11
Protein: p.Val551Glu
Coding: c.1652T>A
MANE Select: NM_017871
Type: single nucleotide variant
Location: chr1:1312103 (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.Val551fs Likely pathogenic same residue
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.Glu554Gly Uncertain significance ★ ⚠ 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-val551glu (accessed [today's date]).

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