Is INTS6 p.Arg876Gln (c.2627G>A) pathogenic?

INTS6 p.Arg876Gln (c.2627G>A) is classified Uncertain significance in INTS6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely benign (0.0848); Very rare (popmax 0.00224%, eas).

How common is INTS6 p.Arg876Gln (c.2627G>A) in the general population?

INTS6 p.Arg876Gln (c.2627G>A) is very rare (popmax 0.00224%, eas) (gnomAD).

What do computational predictors say about INTS6 p.Arg876Gln (c.2627G>A)?

AlphaMissense predicts likely benign (score 0.0848) — an in-silico prediction, not a clinical call.

INTS6 p.Arg876Gln

c.2627G>A · VCV4679150

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0848 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0848	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -5.92	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 13 kb · p 1.5e-11 · regional, not allelic
Overall
CADD	22.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00224% East Asian · 1/44,556 alleles

Filtering AF 0.000125% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.1e-05%

Overall 0.000437% 7/1,601,178 alleles · very rare exomes 6/1,449,400 · genomes 1/151,778 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00224%	44,556
South Asian	0.00112%	89,318
European (non-Finnish)	0.000426%	234,824

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.Arg876Gln
Coding: c.2627G>A
MANE Select: NM_012141
Type: single nucleotide variant
Location: chr13:51365789 (GRCh38)
Gene constraint: LOEUF 0.23 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.80 · 9 PDB
Residue 876: an α-helix

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-arg876gln (accessed [today's date]).

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