Is ELP6 p.Val35Ala (c.104T>C) pathogenic?

ELP6 p.Val35Ala (c.104T>C) is classified Uncertain significance in ELP6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-03-24). AlphaMissense: ambiguous (0.5324); Very rare (popmax 0.00517%, nfe).

How common is ELP6 p.Val35Ala (c.104T>C) in the general population?

ELP6 p.Val35Ala (c.104T>C) is very rare (popmax 0.00517%, nfe) (gnomAD).

What do computational predictors say about ELP6 p.Val35Ala (c.104T>C)?

AlphaMissense predicts ambiguous (score 0.5324) — an in-silico prediction, not a clinical call.

ELP6 p.Val35Ala

c.104T>C · rs778563813 · VCV2510674

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5324 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00517%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5324	ambiguous
REVEL	0.333	indeterminate
SaProt	LLR -7.51	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 18 kb · p 0.24 · regional, not allelic
Overall
CADD	25.9	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 0.00517% European (non-Finnish) · 61/1,179,988 alleles

Filtering AF 0.0041% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00372%

Overall 0.00384% 62/1,614,012 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00517%	19,344
Remaining individualsnot grpmax-eligible	0.0016%	62,482

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: ELP6
Protein: p.Val35Ala
Coding: c.104T>C
MANE Select: NM_001031703
dbSNP: rs778563813
Type: single nucleotide variant
Location: chr3:47511177 (GRCh38)
Gene constraint: LOEUF 1.204 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.70

Full ELP6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ELP6 p.Ala188Gly Uncertain significance ★ ⚠ same type
ELP6 p.Arg123Trp Uncertain significance ★ ⚠ same type
ELP6 p.Arg135Pro Uncertain significance ★ ⚠ same type
ELP6 p.Arg135Trp Uncertain significance ★ ⚠ same type
ELP6 p.Arg209Gln Uncertain significance ★ ⚠ same type
ELP6 p.Arg76Gln Uncertain significance ★ ⚠ same type
ELP6 p.Arg78His Uncertain significance ★ ⚠ same type
ELP6 p.Asn177Thr 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/elp6-p-val35ala (accessed [today's date]).

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