Is EFCAB7 p.Ser323= (c.969C>T) pathogenic?

EFCAB7 p.Ser323= (c.969C>T) is classified Likely benign in EFCAB7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-05). Ultra-rare (popmax 0.0118%, sas).

How common is EFCAB7 p.Ser323= (c.969C>T) in the general population?

EFCAB7 p.Ser323= (c.969C>T) is ultra-rare (popmax 0.0118%, sas) (gnomAD).

EFCAB7 p.Ser323=

c.969C>T · VCV3843622

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0118%, sas)

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 -1.9	GERP -4
Overall
CADD	0.733	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0118% South Asian · 9/76,108 alleles

Filtering AF 0.00615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00451%

Overall 0.00316% 49/1,549,564 alleles · ultra-rare exomes 44/1,398,386 · genomes 5/151,178 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0118%	8,456
Admixed American	0.00951%	10,518
East Asian	0.00464%	21,567
African / African-American	0.00413%	24,193
Remaining individualsnot grpmax-eligible	0.00336%	29,739
European (non-Finnish)	0.00244%	41,058

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: EFCAB7
Protein: p.Ser323=
Coding: c.969C>T
MANE Select: NM_032437
Type: single nucleotide variant
Location: chr1:63551747 (GRCh38)
Gene constraint: LOEUF 1.112 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.62

Full EFCAB7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EFCAB7 p.Phe279Cys Uncertain significance ★★ same type
EFCAB7 p.Asp571Glu Benign ★★ same type
EFCAB7 p.Ser186Gly Benign ★★ same type
EFCAB7 p.Ala472Val Uncertain significance ★ ⚠ same type
EFCAB7 p.Ala9Thr Uncertain significance ★ ⚠ same type
EFCAB7 p.Arg203Trp Uncertain significance ★ ⚠ same type
EFCAB7 p.Arg461Gly Uncertain significance ★ ⚠ same type
EFCAB7 p.Arg475Gly 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/efcab7-p-ser323 (accessed [today's date]).

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