Is EIF3F p.His187= (c.561C>T) pathogenic?

EIF3F p.His187= (c.561C>T) is classified Benign in EIF3F (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-11-27). Common (popmax 84.8%, eas) — too common for a highly-penetrant pathogenic allele; Associated with intellectual developmental disorder, autosomal recessive 67.

What condition is associated with EIF3F p.His187= (c.561C>T)?

EIF3F p.His187= (c.561C>T) is associated with intellectual developmental disorder, autosomal recessive 67 (ClinVar).

EIF3F p.His187=

Q: How common is EIF3F p.His187= (c.561C>T) in the general population?

EIF3F p.His187= (c.561C>T) is common (popmax 84.8%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.561C>T · rs4758267 · VCV1255378

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 84.8%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

intellectual developmental disorder, autosomal recessive 67

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.7	GERP -3.7
Overall
CADD	6.682	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 84.8% East Asian · 38,008/44,842 alleles

Filtering AF 84% ClinGen BA1/BS1 input FAF95, joint · FAF99 83.8%

Overall 71.9% 1,159,722/1,613,468 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	84.8%	1
Admixed American	77.6%	1
Middle Eastern	73.4%	1
European (non-Finnish)	72.9%	1
Remaining individualsnot grpmax-eligible	71.5%	1
Amishnot grpmax-eligible	70.7%	1
South Asian	69.4%	1
Finnishnot grpmax-eligible	68.4%	1
Ashkenazi Jewishnot grpmax-eligible	68%	1
African / African-American	50.7%	2

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: EIF3F
Protein: p.His187=
Coding: c.561C>T
MANE Select: NM_003754
dbSNP: rs4758267
Type: single nucleotide variant
Location: chr11:7992932 (GRCh38)
Gene constraint: LOEUF 0.46 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 75.97 · 29 PDB
Residue 187: the mpn domain; an α-helix

Full EIF3F gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual developmental disorder, autosomal recessive 67 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EIF3F p.Phe232Val Pathogenic/Likely pathogenic ★★ same condition
EIF3F p.Arg306Cys Uncertain significance ★★ ⚠ same condition
EIF3F p.Thr14Met Uncertain significance ★★ ⚠ same condition
EIF3F p.Thr303Ile Uncertain significance ★★ ⚠ same condition
EIF3F c.*24C>T Benign ★★ same condition
EIF3F c.653+3G>T Uncertain significance ★ same condition
EIF3F p.Asn342Ser Uncertain significance ★ ⚠ same condition
EIF3F p.Gly88Asp 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/eif3f-p-his187 (accessed [today's date]).

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