Is INTS11 p.Arg477Trp (c.1429C>T) pathogenic?

INTS11 p.Arg477Trp (c.1429C>T) is classified Uncertain significance in INTS11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-11). AlphaMissense: likely benign (0.2167); Very rare (popmax 0.00998%, nfe).

How common is INTS11 p.Arg477Trp (c.1429C>T) in the general population?

INTS11 p.Arg477Trp (c.1429C>T) is very rare (popmax 0.00998%, nfe) (gnomAD).

What do computational predictors say about INTS11 p.Arg477Trp (c.1429C>T)?

AlphaMissense predicts likely benign (score 0.2167) — an in-silico prediction, not a clinical call.

INTS11 p.Arg477Trp

c.1429C>T · rs762932977 · VCV3110092

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2167 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00998%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2167	likely benign
REVEL	0.231	benign-leaning
SaProt	LLR -12.31	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.3	GERP 1.1, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 13 kb · p 0.087 · regional, not allelic
Overall
CADD	24.0	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

Grpmax group 0.00998% European (non-Finnish) · 116/1,162,442 alleles

Filtering AF 0.00847% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00788%

Overall 0.00799% 126/1,577,822 alleles · very rare exomes 121/1,425,684 · genomes 5/152,138 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00998%	10,021
African / African-American	0.0054%	18,526
South Asian	0.00344%	29,028
Remaining individualsnot grpmax-eligible	0.00327%	30,539
Admixed American	0.00183%	54,700

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.Arg477Trp
Coding: c.1429C>T
MANE Select: NM_017871
dbSNP: rs762932977
Type: single nucleotide variant
Location: chr1:1312475 (GRCh38)
Gene constraint: LOEUF 1.223 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.82 · 15 PDB

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

Similar variants

INTS11 p.Arg477Gln Uncertain significance ★ ⚠ same residue
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

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-arg477trp (accessed [today's date]).

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