Is IER3IP1 p.Phe81= (c.243T>C) pathogenic?

IER3IP1 p.Phe81= (c.243T>C) is classified Likely benign in IER3IP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-23). Very rare (popmax 0.00167%, amr); Associated with microcephaly, epilepsy, and diabetes syndrome.

What condition is associated with IER3IP1 p.Phe81= (c.243T>C)?

IER3IP1 p.Phe81= (c.243T>C) is associated with microcephaly, epilepsy, and diabetes syndrome (ClinVar).

How common is IER3IP1 p.Phe81= (c.243T>C) in the general population?

IER3IP1 p.Phe81= (c.243T>C) is very rare (popmax 0.00167%, amr) (gnomAD).

IER3IP1 p.Phe81=

c.243T>C · VCV3640740

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

microcephaly, epilepsy, and diabetes syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.73 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.6	GERP -1.6, phastCons 1
Overall
CADD	6.52	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,910 alleles

Overall 0.00013% 2/1,537,968 alleles · very rare exomes 2/1,385,658 · genomes 0/152,310 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,910
South Asian	0.00112%	89,314

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: IER3IP1
Protein: p.Phe81=
Coding: c.243T>C
MANE Select: NM_016097
Type: single nucleotide variant
Location: chr18:47156183 (GRCh38)
Gene constraint: LOEUF 1.905 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.57

Full IER3IP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

microcephaly, epilepsy, and diabetes syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

IER3IP1 p.Leu78Pro Pathogenic/Likely pathogenic ★★ ⚠ same condition
IER3IP1 p.Ala74Gly Uncertain significance ★★ ⚠ same condition
IER3IP1 p.Arg57Leu Uncertain significance ★★ ⚠ same condition
IER3IP1 p.Asn54Lys Uncertain significance ★★ ⚠ same condition
IER3IP1 p.Gln10His Uncertain significance ★★ ⚠ same condition
IER3IP1 p.Gly40Cys Uncertain significance ★★ ⚠ same condition
IER3IP1 p.Ile73Thr Uncertain significance ★★ ⚠ same condition
IER3IP1 p.Ile75Val Uncertain significance ★★ ⚠ 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/ier3ip1-p-phe81 (accessed [today's date]).

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