Is ELP1 p.Pro1289Ser (c.3865C>T) pathogenic?

ELP1 p.Pro1289Ser (c.3865C>T) is classified Uncertain significance in ELP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-07). AlphaMissense: ambiguous (0.3967); Ultra-rare (popmax 0.0178%, eas).

How common is ELP1 p.Pro1289Ser (c.3865C>T) in the general population?

ELP1 p.Pro1289Ser (c.3865C>T) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

What do computational predictors say about ELP1 p.Pro1289Ser (c.3865C>T)?

AlphaMissense predicts ambiguous (score 0.3967) — an in-silico prediction, not a clinical call.

ELP1 p.Pro1289Ser

c.3865C>T · rs767316416 · VCV2143891

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3967 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Computational evidence

Protein change
AlphaMissense	0.3967	ambiguous
REVEL	0.371	indeterminate
SaProt	LLR -5.04	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 62 kb · p 0.26 · regional, not allelic
Overall
CADD	26.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0178% East Asian · 8/44,838 alleles

Filtering AF 0.00884% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.000621% 10/1,609,182 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,605
Admixed American	0.00333%	30,001

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: ELP1
Protein: p.Pro1289Ser
Coding: c.3865C>T
MANE Select: NM_003640
dbSNP: rs767316416
Type: single nucleotide variant
Location: chr9:108874961 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.31 · 5 PDB
Residue 1289: the 'mediates dimerization' region

Full ELP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ELP1 p.Pro1289= Likely benign ★ same residue
ELP1 p.Pro1289fs Pathogenic ★ same residue
ELP1 c.1361-1G>T Pathogenic/Likely pathogenic ★★ same type
ELP1 c.1361-2A>G Pathogenic/Likely pathogenic ★★ same type
ELP1 c.1461-1G>A Likely pathogenic ★★ same type
ELP1 c.1644-1G>T Likely pathogenic ★★ same type
ELP1 c.1644-2A>C Likely pathogenic ★★ same type
ELP1 c.1854+1G>A Likely pathogenic ★★ 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/elp1-p-pro1289ser (accessed [today's date]).

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