Is FIGLA p.Phe164= (c.492C>T) pathogenic?

FIGLA p.Phe164= (c.492C>T) is classified Likely benign in FIGLA (ClinVar, Single submitter, 1 submitter; last evaluated 2019-11-08). Very rare (popmax 0.0011%, sas).

How common is FIGLA p.Phe164= (c.492C>T) in the general population?

FIGLA p.Phe164= (c.492C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

FIGLA p.Phe164=

c.492C>T · VCV4955474

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.45	GERP -3.4
Overall
CADD	2.422	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,080 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,613,966 alleles · very rare exomes 5/1,461,706 · genomes 0/152,260 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,080
European (non-Finnish)	0.000339%	294,973

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.Phe164=
Coding: c.492C>T
MANE Select: NM_001004311
Type: single nucleotide variant
Location: chr2:70785532 (GRCh38)
Gene constraint: LOEUF 1.279 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.67

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

Similar variants

FIGLA p.Phe164Cys Uncertain significance ★ ⚠ same residue
FIGLA p.Ala4Glu Uncertain significance ★★ ⚠ same type
FIGLA p.Pro10His Uncertain significance ★★ ⚠ same type
FIGLA p.Pro10Ser Uncertain significance ★★ ⚠ same type
FIGLA p.Thr200Ile Uncertain significance ★★ ⚠ same type
FIGLA p.Val25Met Uncertain significance ★★ ⚠ same type
FIGLA c.231+24T>C Benign ★★ same type
FIGLA c.384+55A>G Benign ★★ 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/figla-p-phe164 (accessed [today's date]).

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