Is EPS8L2 p.Ala554Val (c.1661C>T) pathogenic?

EPS8L2 p.Ala554Val (c.1661C>T) is classified Uncertain significance in EPS8L2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-02-22). AlphaMissense: likely benign (0.0692); No allele count reported in gnomAD v4.1 (AN 1,385,874).

How common is EPS8L2 p.Ala554Val (c.1661C>T) in the general population?

EPS8L2 p.Ala554Val (c.1661C>T) is no allele count reported in gnomAD v4.1 (AN 1,385,874) (gnomAD).

What do computational predictors say about EPS8L2 p.Ala554Val (c.1661C>T)?

AlphaMissense predicts likely benign (score 0.0692) — an in-silico prediction, not a clinical call.

EPS8L2 p.Ala554Val

c.1661C>T · rs1862299576 · VCV1462407

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0692 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,385,874)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0692	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -6.16	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.85	GERP -0.93
Regional constraint	o/e 1.19	unconstrained · MANE · 18 kb · p 2.2e-09 · regional, not allelic
Overall
CADD	7.407	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 and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,385,874). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EPS8L2
Protein: p.Ala554Val
Coding: c.1661C>T
MANE Select: NM_022772
dbSNP: rs1862299576
Type: single nucleotide variant
Location: chr11:725828 (GRCh38)
Gene constraint: LOEUF 1.164 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.67 · 2 PDB

Full EPS8L2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EPS8L2 p.Ala554= Likely benign ★ same residue
EPS8L2 p.Glu165Ter Likely pathogenic ★★ same type
EPS8L2 p.Arg102Trp Uncertain significance ★★ ⚠ same type
EPS8L2 p.Arg193Gln Uncertain significance ★★ ⚠ same type
EPS8L2 p.Arg245Gln Uncertain significance ★★ ⚠ same type
EPS8L2 p.Arg272Trp Uncertain significance ★★ ⚠ same type
EPS8L2 p.Arg365Cys Uncertain significance ★★ ⚠ same type
EPS8L2 p.Arg506Leu 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/eps8l2-p-ala554val (accessed [today's date]).

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