Is ELP3 p.Arg136Ser (c.408A>C) pathogenic?

ELP3 p.Arg136Ser (c.408A>C) is classified Uncertain significance in ELP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-20). AlphaMissense: likely pathogenic (0.9996); Absent from gnomAD v4.1.

How common is ELP3 p.Arg136Ser (c.408A>C) in the general population?

ELP3 p.Arg136Ser (c.408A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ELP3 p.Arg136Ser (c.408A>C)?

AlphaMissense predicts likely pathogenic (score 0.9996) — an in-silico prediction, not a clinical call.

ELP3 p.Arg136Ser

c.408A>C · rs2486740801 · VCV3088514

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9996 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9996	likely pathogenic · top 2% in ELP3
REVEL	0.436	indeterminate
SaProt	LLR -15.47	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 97 kb · p 1.5e-05 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ELP3
Protein: p.Arg136Ser
Coding: c.408A>C
MANE Select: NM_018091
dbSNP: rs2486740801
Type: single nucleotide variant
Location: chr8:28110384 (GRCh38)
Gene constraint: LOEUF 0.936 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.03 · 4 PDB
Residue 136: the radical sam core domain; an α-helix

Full ELP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ELP3 p.Gly278Ser Uncertain significance ★★ ⚠ same type
ELP3 p.Gly50= Benign ★★ same type
ELP3 p.Tyr439= Benign ★★ same type
ELP3 p.Ala46Gly Uncertain significance ★ ⚠ same type
ELP3 p.Ala47Thr Uncertain significance ★ ⚠ same type
ELP3 p.Ala78Val Uncertain significance ★ ⚠ same type
ELP3 p.Arg230Gln Uncertain significance ★ ⚠ same type
ELP3 p.Arg2Lys 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/elp3-p-arg136ser (accessed [today's date]).

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