Is INTS11 p.Phe294= (c.882C>T) pathogenic?

INTS11 p.Phe294= (c.882C>T) is classified Benign in INTS11 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-07-25). Common (popmax 79.5%, nfe) — too common for a highly-penetrant pathogenic allele.

INTS11 p.Phe294=

Q: How common is INTS11 p.Phe294= (c.882C>T) in the general population?

INTS11 p.Phe294= (c.882C>T) is common (popmax 79.5%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.882C>T · rs12142199 · VCV1290897

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 79.5%, nfe) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -4.7	GERP -4
Overall
CADD	0.184	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 79.5% European (non-Finnish) · 937,864/1,179,914 alleles

Filtering AF 79.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 79.3%

Overall 69.8% 1,125,825/1,613,356 alleles · common exomes 1,042,591/1,461,144 · genomes 83,234/152,212 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	81%	1
Amishnot grpmax-eligible	80.8%	1
European (non-Finnish)grpmax	79.5%	1
Finnishnot grpmax-eligible	73%	1
Middle Eastern	71.9%	1
Remaining individualsnot grpmax-eligible	65.3%	2
South Asian	39.9%	3
Admixed American	38.8%	3
African / African-American	15.5%	6
East Asian	1.17%	85

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: INTS11
Protein: p.Phe294=
Coding: c.882C>T
MANE Select: NM_017871
dbSNP: rs12142199
Type: single nucleotide variant
Location: chr1:1313807 (GRCh38)
Gene constraint: LOEUF 1.223 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.82 · 15 PDB
Residue 294: a turn

Full INTS11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

INTS11 p.Phe294Cys Uncertain significance ★ ⚠ same residue
INTS11 c.28+1406C>T Uncertain significance ★★ same type
INTS11 p.Ala241Thr Uncertain significance ★★ ⚠ same type
INTS11 p.Arg231Cys Uncertain significance ★★ ⚠ same type
INTS11 p.Gln467His Uncertain significance ★★ ⚠ same type
INTS11 p.Glu227Lys Uncertain significance ★★ same type
INTS11 p.His157Arg Uncertain significance ★★ ⚠ same type
INTS11 c.1607+18C>A Benign ★★ 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/ints11-p-phe294 (accessed [today's date]).

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