Is ERI1 p.Gln172Ter (c.514C>T) pathogenic?

ERI1 p.Gln172Ter (c.514C>T) is classified Conflicting classifications of pathogenicity in ERI1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-03-03). Absent from gnomAD v4.1; Associated with Hoxha-Aliu syndrome.

What condition is associated with ERI1 p.Gln172Ter (c.514C>T)?

ERI1 p.Gln172Ter (c.514C>T) is associated with Hoxha-Aliu syndrome (ClinVar).

How common is ERI1 p.Gln172Ter (c.514C>T) in the general population?

ERI1 p.Gln172Ter (c.514C>T) is absent from gnomAD v4.1 (gnomAD).

ERI1 p.Gln172Ter

c.514C>T · rs2486243611 · VCV3061999

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,601,788)

Conditions

Hoxha-Aliu syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 7
Splicing
SpliceAI	Δ0.32	acceptor loss, 15 bp away · masked 0 · deltas
Pangolin	Δ0.68	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Overall
CADD	53.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,601,788). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ERI1
Protein: p.Gln172Ter
Coding: c.514C>T
MANE Select: NM_153332
dbSNP: rs2486243611
Type: single nucleotide variant
Location: chr8:9016337 (GRCh38)
Gene constraint: LOEUF 1.526 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.04 · 5 PDB
Residue 172: a UniProt-annotated variant site (in semdgc; likely pathogenic); a UniProt-annotated variant site (in hxal; likely pathogenic); the exonuclease domain; a β-strand

Full ERI1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Hoxha-Aliu syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ERI1 p.Gln172His Uncertain significance ★ ⚠ same residue
ERI1 p.Arg304Ter Likely pathogenic ★ same condition
ERI1 p.Gln244Ter Likely pathogenic ★ same condition
ERI1 p.Lys118Ter Likely pathogenic ★ same condition
ERI1 c.582+1G>A Pathogenic same condition
ERI1 p.Ser333Tyr Uncertain significance ★★ ⚠ same type
ERI1 p.Thr221Ala Uncertain significance ★★ ⚠ same type
ERI1 p.Arg291= 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/eri1-p-gln172ter (accessed [today's date]).

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