Is SLC19A2 p.Ser326Tyr (c.977C>A) pathogenic?

SLC19A2 p.Ser326Tyr (c.977C>A) is classified Uncertain significance in SLC19A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-26). AlphaMissense: likely benign (0.1942); Very rare (popmax 0.00668%, afr).

How common is SLC19A2 p.Ser326Tyr (c.977C>A) in the general population?

SLC19A2 p.Ser326Tyr (c.977C>A) is very rare (popmax 0.00668%, afr) (gnomAD).

What do computational predictors say about SLC19A2 p.Ser326Tyr (c.977C>A)?

AlphaMissense predicts likely benign (score 0.1942) — an in-silico prediction, not a clinical call.

SLC19A2 p.Ser326Tyr

c.977C>A · VCV3392800

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1942 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1942	likely benign
REVEL	0.742	pathogenic-leaning
SaProt	LLR -6.97	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.2	GERP 1.3, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 20 kb · p 0.054 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% African / African-American · 5/74,880 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.000372% 6/1,613,874 alleles · very rare exomes 2/1,461,758 · genomes 4/152,116 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00668%	14,976
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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: SLC19A2
Protein: p.Ser326Tyr
Coding: c.977C>A
MANE Select: NM_006996
Type: single nucleotide variant
Location: chr1:169470017 (GRCh38)
Gene constraint: LOEUF 0.852 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.99 · 2 PDB
Residue 326: a β-strand

Full SLC19A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SLC19A2 p.Ser326Phe Uncertain significance ★ ⚠ same residue
SLC19A2 c.1223+1G>A Pathogenic ★★ same type
SLC19A2 c.807+2T>G Likely pathogenic ★★ same type
SLC19A2 p.Arg162Ter Pathogenic ★★ same type
SLC19A2 p.Arg397Ter Pathogenic/Likely pathogenic ★★ same type
SLC19A2 p.Gln233Ter Pathogenic ★★ same type
SLC19A2 p.Glu66Ter Pathogenic ★★ same type
SLC19A2 p.Gly105Glu Pathogenic/Likely pathogenic ★★ 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/slc19a2-p-ser326tyr (accessed [today's date]).

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