Is ERMP1 p.Ser531= (c.1593G>A) pathogenic?

ERMP1 p.Ser531= (c.1593G>A) is classified Benign in ERMP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). Low-frequency (popmax 2.7%, mid).

How common is ERMP1 p.Ser531= (c.1593G>A) in the general population?

ERMP1 p.Ser531= (c.1593G>A) is low-frequency (popmax 2.7%, mid) (gnomAD).

ERMP1 p.Ser531=

c.1593G>A · rs35643913 · VCV789196

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.7%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.21	acceptor loss · deltas
Constraint at this position
Conservation	phyloP -6.4	GERP -4.9
Overall
CADD	0.768	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.7% Middle Eastern · 163/6,034 alleles

Filtering AF 2.39% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.36%

Overall 0.765% 12,310/1,609,952 alleles · low-frequency

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	3.66%	27
Middle Easterngrpmax	2.7%	37
South Asian	2.48%	40
Remaining individualsnot grpmax-eligible	0.914%	109
European (non-Finnish)	0.665%	150
Admixed American	0.303%	330
Finnishnot grpmax-eligible	0.252%	397
Amishnot grpmax-eligible	0.11%	912
African / African-American	0.0993%	1,007
East Asian	0.0224%	4,461

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ERMP1
Protein: p.Ser531=
Coding: c.1593G>A
MANE Select: NM_024896
dbSNP: rs35643913
Type: single nucleotide variant
Location: chr9:5805741 (GRCh38)
Gene constraint: LOEUF 1.239 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.45

Full ERMP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERMP1 c.1021+6T>C Likely benign ★★ same type
ERMP1 p.Gly809= Benign ★★ same type
ERMP1 p.Val404= Benign ★★ same type
ERMP1 p.Ala109Gly Uncertain significance ★ ⚠ same type
ERMP1 p.Ala109Val Uncertain significance ★ ⚠ same type
ERMP1 p.Ala112Thr Uncertain significance ★ ⚠ same type
ERMP1 p.Ala196Asp Uncertain significance ★ ⚠ same type
ERMP1 p.Ala202Thr 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/ermp1-p-ser531 (accessed [today's date]).

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