Is ECHDC1 p.Ala101Val (c.302C>T) pathogenic?

ECHDC1 p.Ala101Val (c.302C>T) is classified Uncertain significance in ECHDC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-03). AlphaMissense: likely benign (0.1929); Ultra-rare (popmax 0.012%, afr).

How common is ECHDC1 p.Ala101Val (c.302C>T) in the general population?

ECHDC1 p.Ala101Val (c.302C>T) is ultra-rare (popmax 0.012%, afr) (gnomAD).

What do computational predictors say about ECHDC1 p.Ala101Val (c.302C>T)?

AlphaMissense predicts likely benign (score 0.1929) — an in-silico prediction, not a clinical call.

ECHDC1 p.Ala101Val

c.302C>T · VCV3506464

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1929 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1929	likely benign
REVEL	0.527	indeterminate
SaProt	LLR -7.82	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 41 kb · p 0.24 · regional, not allelic
Overall
CADD	25.6	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 and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A107V vs ClinVar A101V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.012% African / African-American · 9/74,728 alleles

Filtering AF 0.00625% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00469%

Overall 0.000558% 9/1,612,792 alleles · ultra-rare

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: ECHDC1
Protein: p.Ala101Val
Coding: c.302C>T
MANE Select: NM_001002030
Type: single nucleotide variant
Location: chr6:127327063 (GRCh38)
Gene constraint: LOEUF 1.452 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.84

Full ECHDC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ECHDC1 p.Met130Thr Likely pathogenic ★ same type
ECHDC1 c.-3+979G>C Uncertain significance ★ ⚠ same type
ECHDC1 p.Ala272Thr Uncertain significance ★ ⚠ same type
ECHDC1 p.Arg192Gln Uncertain significance ★ ⚠ same type
ECHDC1 p.Arg99His Uncertain significance ★ ⚠ same type
ECHDC1 p.Cys262Phe Uncertain significance ★ ⚠ same type
ECHDC1 p.Gln228His Uncertain significance ★ ⚠ same type
ECHDC1 p.Gln274His 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/echdc1-p-ala101val (accessed [today's date]).

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