Is ECD p.Gly77= (c.231C>T) pathogenic?

ECD p.Gly77= (c.231C>T) is classified Likely benign in ECD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-01). Rare (popmax 0.694%, mid).

How common is ECD p.Gly77= (c.231C>T) in the general population?

ECD p.Gly77= (c.231C>T) is rare (popmax 0.694%, mid) (gnomAD).

ECD p.Gly77=

c.231C>T · rs145243678 · VCV2640582

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.694%, 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 0.1	GERP -0.89
Overall
CADD	11.45	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.694% Middle Eastern · 42/6,050 alleles

Filtering AF 0.528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.469%

Overall 0.0265% 426/1,609,910 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.694%	144
African / African-American	0.13%	771
Admixed American	0.0959%	1,043
South Asian	0.0488%	2,048
Remaining individualsnot grpmax-eligible	0.0481%	2,077
Ashkenazi Jewishnot grpmax-eligible	0.0136%	7,371
European (non-Finnish)	0.0129%	7,752

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: ECD
Protein: p.Gly77=
Coding: c.231C>T
MANE Select: NM_006304 · reported on NM_007265
dbSNP: rs145243678
Type: single nucleotide variant
Location: chr10:73160526 (GRCh38)
Structure: AlphaFold pLDDT 69.87 · 140 PDB

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

Similar variants

ECD p.Ala121Gly Uncertain significance ★ same type
ECD p.Ala122Ser Uncertain significance ★ ⚠ same type
ECD p.Ala150Thr Uncertain significance ★ ⚠ same type
ECD p.Ala234Ser Uncertain significance ★ ⚠ same type
ECD p.Ala329Val Uncertain significance ★ ⚠ same type
ECD p.Arg188Leu Uncertain significance ★ ⚠ same type
ECD p.Arg244Gln Uncertain significance ★ ⚠ same type
ECD p.Arg281Gln 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/ecd-p-gly77 (accessed [today's date]).

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