Is FIGLA p.Ile78= (c.234A>T) pathogenic?

FIGLA p.Ile78= (c.234A>T) is classified Benign in FIGLA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2021-05-06). Common (popmax 8.07%, sas) — too common for a highly-penetrant pathogenic allele; Associated with premature ovarian failure 6.

What condition is associated with FIGLA p.Ile78= (c.234A>T)?

FIGLA p.Ile78= (c.234A>T) is associated with premature ovarian failure 6 (ClinVar).

FIGLA p.Ile78=

Q: How common is FIGLA p.Ile78= (c.234A>T) in the general population?

FIGLA p.Ile78= (c.234A>T) is common (popmax 8.07%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.234A>T · rs199650129 · VCV336912

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 8.07%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

premature ovarian failure 6

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 1.8	GERP 0.56, phastCons 1
Overall
CADD	13.86	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.07% South Asian · 7,280/90,246 alleles

Filtering AF 7.91% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.85%

Overall 0.484% 7,799/1,611,756 alleles · common exomes 7,372/1,459,418 · genomes 427/152,338 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	8.07%	12
Remaining individualsnot grpmax-eligible	0.58%	172
Middle Eastern	0.264%	378
African / African-American	0.0227%	4,403
Admixed American	0.0118%	8,502
East Asian	0.0111%	8,974
European (non-Finnish)	0.0095%	10,530

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: FIGLA
Protein: p.Ile78=
Coding: c.234A>T
MANE Select: NM_001004311
dbSNP: rs199650129
Type: single nucleotide variant
Location: chr2:70787799 (GRCh38)
Gene constraint: LOEUF 1.279 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.67
Residue 78: the bhlh domain

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

Disease context

premature ovarian failure 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FIGLA p.Ala4Glu Uncertain significance ★★ ⚠ same condition
FIGLA p.Pro10His Uncertain significance ★★ ⚠ same condition
FIGLA p.Pro10Ser Uncertain significance ★★ ⚠ same condition
FIGLA p.Thr200Ile Uncertain significance ★★ ⚠ same condition
FIGLA p.Val25Met Uncertain significance ★★ ⚠ same condition
FIGLA c.231+24T>C Benign ★★ same condition
FIGLA c.*53A>C Benign/Likely benign ★★ same condition
FIGLA c.*5T>A 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/figla-p-ile78 (accessed [today's date]).

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