Is EMC3 p.Phe248= (c.744C>T) pathogenic?

EMC3 p.Phe248= (c.744C>T) is classified Likely benign in EMC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-01). Ultra-rare (popmax 0.0164%, mid).

How common is EMC3 p.Phe248= (c.744C>T) in the general population?

EMC3 p.Phe248= (c.744C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

EMC3 p.Phe248=

c.744C>T · rs769523238 · VCV2653506

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

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 -5.3	GERP -3.7
Overall
CADD	1.155	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

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

Overall 0.00105% 17/1,613,984 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
East Asian	0.0134%	7,482
Admixed American	0.00167%	59,988
Remaining individualsnot grpmax-eligible	0.0016%	62,490
African / African-American	0.00134%	74,884
South Asian	0.0011%	91,082
European (non-Finnish)	0.000508%	196,672

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: EMC3
Protein: p.Phe248=
Coding: c.744C>T
MANE Select: NM_001394674
dbSNP: rs769523238
Type: single nucleotide variant
Location: chr3:9964111 (GRCh38)
Gene constraint: LOEUF 0.548 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 78.38 · 10 PDB

Full EMC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EMC3 c.-242+3401G>A Uncertain significance ★ same type
EMC3 c.-242+3659C>G Uncertain significance ★ same type
EMC3 p.Ala212Thr Uncertain significance ★ ⚠ same type
EMC3 p.Arg180Trp Uncertain significance ★ ⚠ same type
EMC3 p.Arg57Gln Uncertain significance ★ ⚠ same type
EMC3 p.Arg93Trp Uncertain significance ★ ⚠ same type
EMC3 p.Asn175Ser Uncertain significance ★ ⚠ same type
EMC3 p.Asp41Asn 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/emc3-p-phe248 (accessed [today's date]).

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