Is EYS p.Arg55Ser (c.165A>C) pathogenic?

EYS p.Arg55Ser (c.165A>C) is classified Uncertain significance in EYS (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-27). AlphaMissense: likely benign (0.1485); Very rare (popmax 0.00266%, afr); Associated with Inborn genetic diseases.

What condition is associated with EYS p.Arg55Ser (c.165A>C)?

EYS p.Arg55Ser (c.165A>C) is associated with Inborn genetic diseases (ClinVar).

How common is EYS p.Arg55Ser (c.165A>C) in the general population?

EYS p.Arg55Ser (c.165A>C) is very rare (popmax 0.00266%, afr) (gnomAD).

What do computational predictors say about EYS p.Arg55Ser (c.165A>C)?

AlphaMissense predicts likely benign (score 0.1485) — an in-silico prediction, not a clinical call.

EYS p.Arg55Ser

c.165A>C · VCV4870733

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1485 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00266%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1485	likely benign
REVEL	0.184	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.051	GERP 0.49
Regional constraint	o/e 1.08	unconstrained · MANE · 1,775 kb · p 4.6e-07 · regional, not allelic
Overall
CADD	13.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00266% African / African-American · 2/75,064 alleles

Filtering AF 0.000442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000372% 6/1,614,176 alleles · very rare exomes 6/1,461,844 · genomes 0/152,332 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00266%	37,532
Remaining individualsnot grpmax-eligible	0.0016%	62,508
South Asian	0.0011%	91,088
European (non-Finnish)	0.000169%	590,016

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: EYS
Protein: p.Arg55Ser
Coding: c.165A>C
MANE Select: NM_001142800
Type: single nucleotide variant
Location: chr6:65495246 (GRCh38)
Gene constraint: LOEUF 0.96 · pLI <0.01 (gnomAD)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EYS p.Arg55Ter Likely pathogenic ★ same residue
EYS p.Ala1174Glu Uncertain significance ★★ same condition
EYS p.Ala1465Thr Uncertain significance ★★ ⚠ same condition
EYS p.Ala1520Asp Uncertain significance ★★ ⚠ same condition
EYS p.Ala1520Gly Uncertain significance ★★ ⚠ same condition
EYS p.Ala1984Thr Uncertain significance ★★ same condition
EYS p.Ala2728Val Uncertain significance ★★ ⚠ same condition
EYS p.Ala2729Val 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/eys-p-arg55ser (accessed [today's date]).

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