Is EIF6 p.Arg100Gln (c.299G>A) pathogenic?

EIF6 p.Arg100Gln (c.299G>A) is classified Uncertain significance in EIF6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-09). AlphaMissense: likely pathogenic (0.7131); Ultra-rare (popmax 0.0342%, nfe).

How common is EIF6 p.Arg100Gln (c.299G>A) in the general population?

EIF6 p.Arg100Gln (c.299G>A) is ultra-rare (popmax 0.0342%, nfe) (gnomAD).

What do computational predictors say about EIF6 p.Arg100Gln (c.299G>A)?

AlphaMissense predicts likely pathogenic (score 0.7131) — an in-silico prediction, not a clinical call.

EIF6 p.Arg100Gln

c.299G>A · rs201479805 · VCV2363490

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7131 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0342%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7131	likely pathogenic
REVEL	0.431	indeterminate
SaProt	LLR -13.10	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.2, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 5,287 bp · p 9.4e-05 · regional, not allelic
Overall
CADD	29.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0342% European (non-Finnish) · 404/1,179,916 alleles

Filtering AF 0.0315% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0304%

Overall 0.0257% 415/1,613,910 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0342%	2,921
Remaining individualsnot grpmax-eligible	0.0096%	10,415
Finnishnot grpmax-eligible	0.00625%	16,005
South Asian	0.0011%	91,010

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: EIF6
Protein: p.Arg100Gln
Coding: c.299G>A
MANE Select: NM_002212
dbSNP: rs201479805
Type: single nucleotide variant
Location: chr20:35280724 (GRCh38)
Gene constraint: LOEUF 0.623 · pLI 0.65 (gnomAD)
Structure: AlphaFold pLDDT 91.12 · 48 PDB

Full EIF6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EIF6 p.Ala183Thr Uncertain significance ★ ⚠ same type
EIF6 p.Arg85Cys Uncertain significance ★ ⚠ same type
EIF6 p.Arg85His Uncertain significance ★ ⚠ same type
EIF6 p.Asn156Ser Uncertain significance ★ ⚠ same type
EIF6 p.Asn9Thr Uncertain significance ★ ⚠ same type
EIF6 p.Asp144Asn Uncertain significance ★ ⚠ same type
EIF6 p.Asp78Asn Uncertain significance ★ ⚠ same type
EIF6 p.Glu124Val 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/eif6-p-arg100gln (accessed [today's date]).

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