Is ERICH6 p.Phe367Leu (c.1101C>A) pathogenic?

ERICH6 p.Phe367Leu (c.1101C>A) is classified Uncertain significance in ERICH6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-05). AlphaMissense: ambiguous (0.4002); Ultra-rare (popmax 0.0134%, eas).

How common is ERICH6 p.Phe367Leu (c.1101C>A) in the general population?

ERICH6 p.Phe367Leu (c.1101C>A) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about ERICH6 p.Phe367Leu (c.1101C>A)?

AlphaMissense predicts ambiguous (score 0.4002) — an in-silico prediction, not a clinical call.

ERICH6 p.Phe367Leu

c.1101C>A · VCV4250810

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4002 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4002	ambiguous
REVEL	0.025	moderately benign-leaning
SaProt	LLR -5.05	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.79	GERP -3.4
Regional constraint	o/e 1.03	unconstrained · MANE · 44 kb · p 0.37 · regional, not allelic
Overall
CADD	0.091	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 0.0134% East Asian · 6/44,896 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.000434% 7/1,614,026 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,483
European (non-Finnish)	8.47e-05%	1,179,998

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: ERICH6
Protein: p.Phe367Leu
Coding: c.1101C>A
MANE Select: NM_152394
Type: single nucleotide variant
Location: chr3:150680478 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.73

Full ERICH6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERICH6 p.Phe367Tyr Uncertain significance ★ ⚠ same residue
ERICH6 p.Ala320Gly Uncertain significance ★ ⚠ same type
ERICH6 p.Ala354Val Uncertain significance ★ ⚠ same type
ERICH6 p.Ala479Ser Uncertain significance ★ ⚠ same type
ERICH6 p.Ala562Ser Uncertain significance ★ ⚠ same type
ERICH6 p.Arg374Cys Uncertain significance ★ ⚠ same type
ERICH6 p.Arg414Pro Uncertain significance ★ ⚠ same type
ERICH6 p.Arg414Trp 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/erich6-p-phe367leu (accessed [today's date]).

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