Is ERC1 p.Gln16His (c.48G>C) pathogenic?

ERC1 p.Gln16His (c.48G>C) is classified Benign in ERC1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-17). AlphaMissense: likely benign (0.1391); Low-frequency (popmax 2.05%, eas); Associated with ERC1-related disorder.

What condition is associated with ERC1 p.Gln16His (c.48G>C)?

ERC1 p.Gln16His (c.48G>C) is associated with ERC1-related disorder (ClinVar).

How common is ERC1 p.Gln16His (c.48G>C) in the general population?

ERC1 p.Gln16His (c.48G>C) is low-frequency (popmax 2.05%, eas) (gnomAD).

What do computational predictors say about ERC1 p.Gln16His (c.48G>C)?

AlphaMissense predicts likely benign (score 0.1391) — an in-silico prediction, not a clinical call.

ERC1 p.Gln16His

c.48G>C · rs61740169 · VCV3033364

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1391 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.05%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

ERC1-related disorder

Computational evidence

Protein change
AlphaMissense	0.1391	likely benign
REVEL	0.294	indeterminate
SaProt	LLR -6.29	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 8.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 462 kb · p 5.7e-05 · regional, not allelic
Overall
CADD	24.1	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 2.05% East Asian · 920/44,860 alleles

Filtering AF 1.94% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9%

Overall 0.0707% 1,141/1,613,490 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	2.05%	49
Remaining individualsnot grpmax-eligible	0.146%	687
South Asian	0.118%	851
African / African-American	0.0107%	9,378
Admixed American	0.00333%	30,005
European (non-Finnish)	0.0011%	90,730

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: ERC1
Protein: p.Gln16His
Coding: c.48G>C
MANE Select: NM_178040
dbSNP: rs61740169
Type: single nucleotide variant
Location: chr12:1027951 (GRCh38)
Gene constraint: LOEUF 0.503 · pLI 0.79 (gnomAD)
Structure: AlphaFold pLDDT 75.64
Residue 16: the 'disordered' region

Full ERC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ERC1-related disorder

Similar variants

ERC1 c.1738-6A>C Likely benign same condition
ERC1 c.2158-4G>A Benign same condition
ERC1 c.3214-9201G>T Likely benign same condition
ERC1 c.3214-9246C>T Benign same condition
ERC1 p.Ala940= Benign same condition
ERC1 p.Arg103Pro Likely benign ⚠ same condition
ERC1 p.His342= Likely benign same condition
ERC1 p.Ile629Val Benign ⚠ same condition

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/erc1-p-gln16his (accessed [today's date]).

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