Is ECHS1 p.Phe27Val (c.79T>G) pathogenic?

ECHS1 p.Phe27Val (c.79T>G) is classified Uncertain significance in ECHS1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-09-28). AlphaMissense: likely benign (0.1161); Ultra-rare (popmax 0.0803%, afr).

How common is ECHS1 p.Phe27Val (c.79T>G) in the general population?

ECHS1 p.Phe27Val (c.79T>G) is ultra-rare (popmax 0.0803%, afr) (gnomAD).

What do computational predictors say about ECHS1 p.Phe27Val (c.79T>G)?

AlphaMissense predicts likely benign (score 0.1161) — an in-silico prediction, not a clinical call.

ECHS1 p.Phe27Val

c.79T>G · rs900684601 · VCV1511505

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1161 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0803%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1161	likely benign
REVEL	0.162	moderately benign-leaning
SaProt	LLR -6.52	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 10 kb · p 0.4 · regional, not allelic
Overall
CADD	21.9	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

Grpmax group 0.0803% African / African-American · 54/67,262 alleles

Filtering AF 0.0632% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.057%

Overall 0.00409% 59/1,440,924 alleles · ultra-rare exomes 27/1,288,968 · genomes 32/151,956 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0803%	1,246
Remaining individualsnot grpmax-eligible	0.00718%	13,918
Admixed American	0.00286%	34,948

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: ECHS1
Protein: p.Phe27Val
Coding: c.79T>G
MANE Select: NM_004092
dbSNP: rs900684601
Type: single nucleotide variant
Location: chr10:133373255 (GRCh38)
Gene constraint: LOEUF 0.907 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.54 · 6 PDB

Full ECHS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ECHS1 c.414+1G>A Pathogenic/Likely pathogenic ★★ same type
ECHS1 c.88+5G>A Pathogenic/Likely pathogenic ★★ same type
ECHS1 p.Ala132Thr Pathogenic/Likely pathogenic ★★ same type
ECHS1 p.Ala173Val Pathogenic/Likely pathogenic ★★ same type
ECHS1 p.Ala238Val Pathogenic/Likely pathogenic ★★ ⚠ same type
ECHS1 p.Ala278Thr Likely pathogenic ★★ same type
ECHS1 p.Ala2Val Pathogenic ★★ same type
ECHS1 p.Arg54Cys Pathogenic/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/echs1-p-phe27val (accessed [today's date]).

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