Is INTS6 p.Asp518= (c.1554C>T) pathogenic?

INTS6 p.Asp518= (c.1554C>T) is classified Likely benign in INTS6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-11). Low-frequency (popmax 1.57%, eas); Associated with INTS6-related disorder.

What condition is associated with INTS6 p.Asp518= (c.1554C>T)?

INTS6 p.Asp518= (c.1554C>T) is associated with INTS6-related disorder (ClinVar).

How common is INTS6 p.Asp518= (c.1554C>T) in the general population?

INTS6 p.Asp518= (c.1554C>T) is low-frequency (popmax 1.57%, eas) (gnomAD).

INTS6 p.Asp518=

c.1554C>T · rs140156322 · VCV3049141

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.57%, eas)

Conditions

INTS6-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -4.1, phastCons 1
Overall
CADD	5.46	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.57% East Asian · 704/44,834 alleles

Filtering AF 1.47% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.44%

Overall 0.0522% 843/1,613,404 alleles · low-frequency exomes 722/1,461,282 · genomes 121/152,122 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	1.57%	64
Remaining individualsnot grpmax-eligible	0.139%	718
South Asian	0.0417%	2,396
Middle Eastern	0.0165%	6,054
Admixed American	0.01%	10,000
European (non-Finnish)	0.000593%	168,495

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: INTS6
Protein: p.Asp518=
Coding: c.1554C>T
MANE Select: NM_012141
dbSNP: rs140156322
Type: single nucleotide variant
Location: chr13:51378287 (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

Disease context

INTS6-related disorder

Similar variants

INTS6 p.Gln228Glu Likely pathogenic ★ same condition
INTS6 p.Val381Gly Uncertain significance ★ ⚠ same condition
INTS6 c.1275+1G>A Uncertain significance same condition
INTS6 p.Arg550Ter Uncertain significance same condition
INTS6 p.Gly30= Uncertain significance same condition
INTS6 c.340-3T>C Benign same condition
INTS6 p.Ala738Gly Likely benign same condition
INTS6 p.Leu845= Likely benign 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/ints6-p-asp518 (accessed [today's date]).

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