Is EPS8 p.Ser551= (c.1653G>A) pathogenic?

EPS8 p.Ser551= (c.1653G>A) is classified Benign/Likely benign in EPS8 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-18). Low-frequency (popmax 1.32%, mid); Associated with autosomal recessive nonsyndromic hearing loss 102.

What condition is associated with EPS8 p.Ser551= (c.1653G>A)?

EPS8 p.Ser551= (c.1653G>A) is associated with autosomal recessive nonsyndromic hearing loss 102 (ClinVar).

How common is EPS8 p.Ser551= (c.1653G>A) in the general population?

EPS8 p.Ser551= (c.1653G>A) is low-frequency (popmax 1.32%, mid) (gnomAD).

EPS8 p.Ser551=

c.1653G>A · rs75362705 · VCV509187

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.32%, mid)

Conditions

autosomal recessive nonsyndromic hearing loss 102

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 -15	GERP -4.8
Overall
CADD	0.117	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.32% Middle Eastern · 78/5,910 alleles

Filtering AF 1.08% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.06%

Overall 0.449% 7,090/1,578,408 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.32%	76
South Asian	1.14%	88
Remaining individualsnot grpmax-eligible	0.507%	197
European (non-Finnish)	0.468%	214
Admixed American	0.251%	399
Finnishnot grpmax-eligible	0.125%	799
Ashkenazi Jewishnot grpmax-eligible	0.0934%	1,071
African / African-American	0.0653%	1,531
East Asian	0.0161%	6,193

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.Ser551=
Coding: c.1653G>A
MANE Select: NM_004447
dbSNP: rs75362705
Type: single nucleotide variant
Location: chr12:15641746 (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 551: the sh3 domain

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

Disease context

autosomal recessive nonsyndromic hearing loss 102 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EPS8 c.205-8A>G Uncertain significance ★★ same condition
EPS8 p.Ala150Val Uncertain significance ★★ ⚠ same condition
EPS8 p.Arg702Trp Uncertain significance ★★ ⚠ same condition
EPS8 p.Leu329Pro Uncertain significance ★★ ⚠ same condition
EPS8 p.Thr726Ile Uncertain significance ★★ ⚠ same condition
EPS8 p.His35Arg Benign/Likely benign ★★ same condition
EPS8 c.1435-2A>T Likely pathogenic ★ same condition
EPS8 c.517-1G>T Pathogenic ★ 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/eps8-p-ser551 (accessed [today's date]).

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