Is INTS6 p.Lys641Ile (c.1922A>T) pathogenic?

INTS6 p.Lys641Ile (c.1922A>T) is classified Uncertain significance in INTS6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-15). AlphaMissense: likely pathogenic (0.8865); Absent from gnomAD v4.1.

How common is INTS6 p.Lys641Ile (c.1922A>T) in the general population?

INTS6 p.Lys641Ile (c.1922A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about INTS6 p.Lys641Ile (c.1922A>T)?

AlphaMissense predicts likely pathogenic (score 0.8865) — an in-silico prediction, not a clinical call.

INTS6 p.Lys641Ile

c.1922A>T · VCV4836647

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8865 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8865	likely pathogenic
REVEL	0.217	benign-leaning
SaProt	LLR -6.73	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 13 kb · p 1.5e-11 · regional, not allelic
Overall
CADD	27.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: INTS6
Protein: p.Lys641Ile
Coding: c.1922A>T
MANE Select: NM_012141
Type: single nucleotide variant
Location: chr13:51374390 (GRCh38)
Gene constraint: LOEUF 0.23 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.80 · 9 PDB

Full INTS6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

INTS6 p.Thr749Ala Benign ★★ same type
INTS6 p.Arg206Cys Likely pathogenic ★ same type
INTS6 p.Arg610Ter Pathogenic ★ same type
INTS6 p.Gln185Ter Pathogenic ★ same type
INTS6 p.Gln228Glu Likely pathogenic ★ same type
INTS6 c.613+2T>C Uncertain significance ★ same type
INTS6 p.Ala44Gly Uncertain significance ★ ⚠ same type
INTS6 p.Ala530Ser Uncertain significance ★ ⚠ 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/ints6-p-lys641ile (accessed [today's date]).

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