Is INTS6 p.Ala738Gly (c.2213C>G) pathogenic?

INTS6 p.Ala738Gly (c.2213C>G) is classified Likely benign in INTS6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-02-19). AlphaMissense: likely benign (0.0768); Rare (popmax 0.444%, eas); Associated with INTS6-related disorder.

What condition is associated with INTS6 p.Ala738Gly (c.2213C>G)?

INTS6 p.Ala738Gly (c.2213C>G) is associated with INTS6-related disorder (ClinVar).

How common is INTS6 p.Ala738Gly (c.2213C>G) in the general population?

INTS6 p.Ala738Gly (c.2213C>G) is rare (popmax 0.444%, eas) (gnomAD).

What do computational predictors say about INTS6 p.Ala738Gly (c.2213C>G)?

AlphaMissense predicts likely benign (score 0.0768) — an in-silico prediction, not a clinical call.

INTS6 p.Ala738Gly

c.2213C>G · rs199886113 · VCV3034812

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0768 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.444%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

INTS6-related disorder

Computational evidence

Protein change
AlphaMissense	0.0768	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -6.34	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 9.7	GERP 1.4, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 13 kb · p 1.5e-11 · regional, not allelic
Overall
CADD	18.88	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 0.444% East Asian · 199/44,852 alleles

Filtering AF 0.393% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.374%

Overall 0.0184% 297/1,613,848 alleles · rare exomes 259/1,461,556 · genomes 38/152,292 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.444%	225
Remaining individualsnot grpmax-eligible	0.126%	791
African / African-American	0.0147%	6,819
Admixed American	0.00333%	29,994
South Asian	0.0022%	45,543
European (non-Finnish)	0.000339%	294,963

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.Ala738Gly
Coding: c.2213C>G
MANE Select: NM_012141
dbSNP: rs199886113
Type: single nucleotide variant
Location: chr13:51369202 (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.Asp518= 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-ala738gly (accessed [today's date]).

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