Is INTS8 p.Gly437Glu (c.1310G>A) pathogenic?

INTS8 p.Gly437Glu (c.1310G>A) is classified Likely benign in INTS8 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-09-01). AlphaMissense: likely benign (0.077); Rare (popmax 0.701%, nfe).

How common is INTS8 p.Gly437Glu (c.1310G>A) in the general population?

INTS8 p.Gly437Glu (c.1310G>A) is rare (popmax 0.701%, nfe) (gnomAD).

What do computational predictors say about INTS8 p.Gly437Glu (c.1310G>A)?

AlphaMissense predicts likely benign (score 0.077) — an in-silico prediction, not a clinical call.

INTS8 p.Gly437Glu

c.1310G>A · rs148690736 · VCV789298

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.077 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.701%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.077	likely benign
REVEL	0.105	moderately benign-leaning
SaProt	LLR -5.78	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 -0.21	GERP -1.2, phastCons 0.034
Regional constraint	o/e 0.85	unconstrained · MANE · 57 kb · p 2.4e-07 · regional, not allelic
Overall
CADD	14.45	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 0.701% European (non-Finnish) · 8,058/1,149,258 alleles

Filtering AF 0.688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.683%

Overall 0.574% 8,977/1,563,984 alleles · rare exomes 8,306/1,411,978 · genomes 671/152,006 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.701%	143
Remaining individualsnot grpmax-eligible	0.513%	195
Finnishnot grpmax-eligible	0.285%	351
Admixed American	0.251%	399
Ashkenazi Jewishnot grpmax-eligible	0.205%	488
South Asian	0.179%	558
African / African-American	0.107%	931
Middle Eastern	0.0169%	5,932
East Asian	0.00456%	21,928

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: INTS8
Protein: p.Gly437Glu
Coding: c.1310G>A
MANE Select: NM_017864
dbSNP: rs148690736
Type: single nucleotide variant
Location: chr8:94849511 (GRCh38)
Gene constraint: LOEUF 0.453 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 84.47 · 10 PDB
Residue 437: an α-helix

Full INTS8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

INTS8 p.Tyr499Cys Uncertain significance ★★ ⚠ same type
INTS8 c.1018-11G>A Benign ★★ same type
INTS8 p.Ala898= Benign ★★ same type
INTS8 p.His922= Benign ★★ same type
INTS8 p.Ser710= Benign ★★ same type
INTS8 p.Ser755Arg Benign/Likely benign ★★ ⚠ same type
INTS8 p.Arg359Ter Likely pathogenic ★ same type
INTS8 c.2762+1G>A 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/ints8-p-gly437glu (accessed [today's date]).

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