Is ERICH6B p.Ala648= (c.1944C>G) pathogenic?

ERICH6B p.Ala648= (c.1944C>G) is classified Likely benign in ERICH6B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-01). Rare (popmax 0.433%, afr).

How common is ERICH6B p.Ala648= (c.1944C>G) in the general population?

ERICH6B p.Ala648= (c.1944C>G) is rare (popmax 0.433%, afr) (gnomAD).

ERICH6B p.Ala648=

c.1944C>G · rs369978802 · VCV2643800

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.433%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.2	GERP -3
Overall
CADD	0.055	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.433% African / African-American · 317/73,128 alleles

Filtering AF 0.394% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.379%

Overall 0.0275% 426/1,551,618 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.433%	231
Admixed American	0.102%	981
Remaining individualsnot grpmax-eligible	0.0599%	1,670
Middle Eastern	0.0169%	5,928
European (non-Finnish)	0.00166%	60,369
South Asian	0.00119%	84,038

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: ERICH6B
Protein: p.Ala648=
Coding: c.1944C>G
MANE Select: NM_182542
dbSNP: rs369978802
Type: single nucleotide variant
Location: chr13:45541609 (GRCh38)
Gene constraint: LOEUF 1.023 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 51.67

Full ERICH6B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERICH6B p.Ala193Asp Uncertain significance ★ ⚠ same type
ERICH6B p.Ala285Thr Uncertain significance ★ ⚠ same type
ERICH6B p.Ala531Ser Uncertain significance ★ ⚠ same type
ERICH6B p.Ala580Val Uncertain significance ★ ⚠ same type
ERICH6B p.Ala665Thr Uncertain significance ★ ⚠ same type
ERICH6B p.Arg226Cys Uncertain significance ★ ⚠ same type
ERICH6B p.Arg226His Uncertain significance ★ ⚠ same type
ERICH6B p.Arg415Cys 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/erich6b-p-ala648 (accessed [today's date]).

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