Is EPS8 p.Thr71= (c.213T>C) pathogenic?

EPS8 p.Thr71= (c.213T>C) is classified Benign in EPS8 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-20). Low-frequency (popmax 3.25%, afr).

How common is EPS8 p.Thr71= (c.213T>C) in the general population?

EPS8 p.Thr71= (c.213T>C) is low-frequency (popmax 3.25%, afr) (gnomAD).

EPS8 p.Thr71=

c.213T>C · rs2230644 · VCV517549

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.25%, afr)

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 -0.14	GERP -4.1, phastCons 0.01
Overall
CADD	4.264	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.25% African / African-American · 2,403/73,982 alleles

Filtering AF 3.14% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.1%

Overall 0.183% 2,926/1,595,590 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.25%	31
Remaining individualsnot grpmax-eligible	0.293%	341
Admixed American	0.277%	361
Middle Eastern	0.202%	496
European (non-Finnish)	0.0145%	6,899
South Asian	0.0068%	14,707
East Asian	0.00224%	44,682

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: EPS8
Protein: p.Thr71=
Coding: c.213T>C
MANE Select: NM_004447
dbSNP: rs2230644
Type: single nucleotide variant
Location: chr12:15669817 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 70.77 · 2 PDB
Residue 71: the ptb domain

Full EPS8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EPS8 c.205-8A>G Uncertain significance ★★ same type
EPS8 p.Ala150Val Uncertain significance ★★ ⚠ same type
EPS8 p.Ala219Val Uncertain significance ★★ ⚠ same type
EPS8 p.Ala416Asp Uncertain significance ★★ ⚠ same type
EPS8 p.Arg195Trp Uncertain significance ★★ ⚠ same type
EPS8 p.Arg403Trp Uncertain significance ★★ ⚠ same type
EPS8 p.Arg432Gln Uncertain significance ★★ ⚠ same type
EPS8 p.Arg434Cys 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/eps8-p-thr71 (accessed [today's date]).

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